Phenylamino isothiazole carboxamidines as MEK inhibitors

ABSTRACT

The invention concerns compounds which inhibit MEK and which have activity as anti-neoplastic agents. These compounds include N-substituted-3-hydroxy-5-arylamino-isothiazole-4-carboxamidines. Also included are the tautomeric isothiazol-3(2H)-ones.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/645,425, filed Jan. 20, 2005; U.S. Provisional Application No.60/653,340, filed Feb. 16, 2005; U.S. Provisional Application No.60/675,395, filed Apr. 27, 2005; U.S. Provisional Application No.60/685,131, filed May 26, 2005; U.S. Provisional Application No.60/685,194, filed May 26, 2005; U.S. Provisional Application No.60/688,005, filed Jun. 6, 2005; U.S. Provisional Application No.60/688,006, filed Jun. 6, 2005; U.S. Provisional Application No.60/688,628, filed Jun. 7, 2005; and U.S. Provisional Application No.60/691,698, filed Jun. 16, 2005. All of these applications are herebyincorporated herein by reference.

FIELD OF THE INVENTION

The invention concerns compounds which inhibit MEK and which haveactivity as anti-neoplastic agents. These compounds includeN-substituted-3-hydroxy-5-aryl-isothiazole-4-carboxamidines. Alsoincluded are the tautomeric isothiazol-3(2H)-ones.

BACKGROUND OF THE INVENTION

Oncogenes—genes that contribute to the production of cancers—aregenerally mutated forms of certain normal cellular genes(“proto-oncogenes”). Oncogenes often encode abnormal versions of signalpathway components, such as receptor tyrosine kinases, serine-threoninekinases, or downstream signaling molecules. The central downstreamsignaling molecules are the Ras proteins, which are anchored on theinner surfaces of cytoplasmic membranes, and which hydrolyze boundguanosine triphosphate (GTP) to guanosine diphosphate (GDP). Whenactivated by a growth factor, growth factor receptors initiate a chainof reactions that leads to the activation of guanine nucleotide exchangeactivity on Ras. Ras alternates between an active “on” state with abound GTP (hereafter “Ras.GTP”) and an inactive “off” state with a boundGDP. The active “on” state, Ras.GTP, binds to and activates proteinsthat control the growth and differentiation of cells.

For example, in the “mitogen-activated protein kinase (MAP kinase)cascade,” Ras.GTP leads to the activation of a cascade ofserine/threonine kinases. One of several groups of kinases known torequire a Ras.GTP for their own activation is the Raf family. The Rafproteins activate “MEK1” and “MEK2,” abbreviations for mitogen-activatedERK-activating kinases (where ERK is extracellular signal-regulatedprotein kinase, another designation for MAPK). MEK1 and MEK2 aredual-function serine/threonine and tyrosine protein kinases and are alsoknown as MAP kinase kinases. Thus, Ras.GTP activates Raf, whichactivates MEK1 and MEK2, which activate MAP kinase (MAPK). Activation ofMAP kinase by mitogens appears to be essential for proliferation, andconstitutive activation of this kinase is sufficient to induce cellulartransformation. Blockade of downstream Ras signaling, as by use of adominant negative Raf-1 protein, can completely inhibit mitogenesis,whether induced from cell surface receptors or from oncogenic Rasmutants.

The interaction of Raf and Ras is a key regulatory step in the controlof cell proliferation. To date, no substrates of MEK other than MAPKhave been identified; however, recent reports indicate that MEK may alsobe activated by other upstream signal proteins such as MEK kinase orMEKK1 and PKC. Activated MAPK translocates and accumulates in thenucleus, where it can phosphorylate and activate transcription factorssuch as Elk-1 and Sap1a, leading to the enhanced expression of genessuch as that for c-fos.

Once activated, Raf and other kinases phosphorylate MEK on twoneighboring serine residues, S²¹⁸ and S²²² in the case of MEK-1. Thesephosphorylations are required for activation of MEK as a kinase. Inturn, MEK phosphorylates MAP kinase on two residues separated by asingle amino acid: a tyrosine, Y¹⁸⁵, and a threonine, T¹⁸³. MEK appearsto associate strongly with MAP kinase prior to phosphorylating it,suggesting that phosphorylation of MAP kinase by MEK may require a priorstrong interaction between the two proteins. Two factors—MEK's unusualspecificity and its requirement for a strong interaction with MAP kinaseprior to phosphorylation—suggest that MEK's mechanism of action maydiffer sufficiently from the mechanisms of other protein kinases as toallow for selective inhibitors of MEK. Possibly, such inhibitors wouldoperate through allosteric mechanisms rather than through the more usualmechanism involving blockage of an ATP binding site.

MEK1 and MEK2 are, therefore, validated and accepted targets foranti-proliferative therapies, even when the oncogenic mutation does notaffect MEK structure or expression. See, e.g., U.S. Patent Publications2003/0149015 by Barrett et al. and 2004/0029898 by Boyle et al.

An N-unsubstituted,3-hydroxy-5-phenyoxyphenyl-isothiazole-4-carboxyamidine having anti MEKactivity was described in a patent publication commonly assigned withthe present application. US 2004/0039037 (Feb. 26, 2004). No analogs orderivatives of the compound were described. A group of3-phenyloxy-5-alkylureido-isothiazole-4-carboxamide kinase inhibitorshaving anti-proliferative activity was reported in U.S. Pat. No.6,548,526 and No. 6,235,764. These compounds were not noted to be MEKinhibitors; they inhibited a tyrosine kinase activity associated withthe vascular endothelial growth factor receptor (VEGF).

A second group of isothiazole-4-carboxamides with anti-proliferativeactivity via blockage of Trk tyrosine kinase—not a VEGF-associatedkinase—was described in U.S. Patent Publication 2004/0152691. Thecompounds are 3-arylsulfanyl-5-heteroarylamino-isothiazoles.

Isoxazole inhibitors of MEK-activated kinase (ERK or MAPK) weredescribed in U.S. Pat. No. 6,649,640 and No. 6,495,582. Rather than3-hydroxy-4-carboxamides or 3-hydroxy-4-carboxamidines, the compoundsdisclosed in these patents are 3-unsubstituted or 3-aminosubstituted-4-aryl isoxazoles.

BRIEF DESCRIPTION OF THE INVENTION

In general, this invention provides a compound of formula I

where Ar¹ is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, inwhich all ring carbon atoms are optionally substituted with substituentsR₁, R₂, and R₃, where R₁, R₂, and R₃ are selected independently fromhydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl;C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₃-C₆ cycloalkyl; C₅-C₆ cycloalkenyl,C₅-C₆ cycloalkadienyl, O—C₁-C₆ alkyl, O—C₂-C₆ alkenyl, C₁-C₆alkyl-C(═O)—, C₁-C₆ alkenyl-C(═O)—, C₁-C₆ alkyl-O—C(═O)—, C₁-C₆alkenyl-O—C(═O)—, C₁-C₆ alkyl-C(═O)—O—, C₁-C₆ alkenyl-C(═O)—O—,isothiazolyl, isoxazolyl, oxazolyl, oxazolidyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, phenyl, CH₃SO₂—, NH₂SO₂—, CH₃NHSO₂—, CH₃SO₂NH—,R₇R₈N—, R₈R₉NCH₂—, R₇C(═O)NH, —S(O)₂NR₇R₈, or R₇R₈NC(═O), wherein R₇-R₉are, independently, H, C₁-C₄ alkyl, phenyl, or C₂-C₆ alkenyl; R₁₀—C≡C—,wherein R₁₀ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₃-C₆ cycloalkyl, C₅-C₆cycloalkenyl, (CH₃)₂NCH₂—, phenyl or (CH₃)₂NCH₂CH₂—; R₄ is H, C₁-C₃alkyl, or C₁-C₃ alkenyl, said alkyl and said alkenyl groups optionallysubstituted with, independently, 1, 2, or 3 halogen atoms, O—C₁₋₂ alkyl,C₁-C₃ alkenyl, and N(H)C₁₋₂ alkyl; R₅ is H or C₁-C₃ alkyl; and in whichall alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, and heteroarylgroups in R₁-R₁₀ are optionally substituted with one, two, or threegroups selected from F, Cl, Br, I, OH, CN, C₁-C₄ alkyl, C₁-C₄ alkoxyl,and C₂-C₄ alkenyl; or any of the pairs R₁ and R₂, R₇ and R₈, or R₈ andR₉ are attached to adjacent carbons and, together with the ring atoms towhich they are attached, form an additional, fused, five- orsix-membered ring, optionally containing one or two heteroatoms selectedfrom O, N, and S, which ring may be aromatic or aliphatic; wherein allalkyl, alkenyl, and cycloalkyl groups and all rings are optionallysubstituted with 1-3 halogen atoms, and all rings are also optionallysubstituted with 1-3 C₁-C₃ alkyl groups or trifluoromethyl groups;

-   A is O, S, CH₂, N₂, C(O), NHC(O), C(O)CH₂, or CH₂C(O);-   or Ar¹-A is

where the five-membered ring is fused to Ar¹ and Y is NH, S, or O,

-   or Ar¹-A is

where the dotted line represents an optional double bond, thefive-membered ring is fused to Ar¹, and R_(x) is selected fromsubstituents listed above for R₃;

-   or Ar¹-A is

where the five-membered ring is fused to Ar¹, and R_(x) is selected fromsubstituents listed above for R₃;

-   Ar² is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, where    ring carbon atoms are optionally substituted with substituents    R₄-R₆, where R₄ is defined as for R₁-R₃ above; R₅ and R₆ are,    independently, H, F, Cl, Br, CH₃, or CF₃; and in which all alkyl,    cycloalkyl, alkenyl, cycloalkenyl, aryl, and heteroaryl groups in    R₁-R₉ are optionally substituted with one, two, or three groups    selected from F, Cl, Br, I, OH, CN, C₁-C₄ alkyl, C₁-C₄ alkoxyl, and    C₂-C₄ alkenyl; which are selected independently from H, F, Cl, Br,    CH₃, or CF₃;-   or Ar²—NH— is

where R_(y) is selected from substituents listed above for R₃;

-   and R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups    optionally substituted with one to three groups selected    independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B    or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉    bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,    tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl,    where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,    piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are    optionally substituted with one to three groups selected    independently from hydroxy, halogen, and methyl;-   or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or    six-membered ring or a 9-14-membered fused ring system, wherein each    ring optionally contains 1-3 heteroatoms selected independently from    O, N, and S; wherein each ring is optionally substituted with 1-3    groups selected independently from the following: halogen, hydroxy,    cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is    optionally substituted with one to three halogen atoms; and wherein    each ring optionally contains one or more double bonds;-   or R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl,    indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and    adamantin-1-yl.

In one generic embodiment, this invention provides a compound of formulaI where Ar¹ and Ar² are both 6-membered rings.

In another generic embodiment, this invention provides a compound offormula I in which A is S, CH₂, N₂, CO, C(O)CH₂, or NHC(O).

In another generic embodiment, this invention provides a compound offormula I, in which A is O, C(O), or CH₂C(O).

In another generic embodiment, this invention provides a compound offormula I where R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkylgroups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl, saidphenyl group or groups optionally substituted with one to three groupsselected independently from hydroxy, halogen, and methyl.

In another generic embodiment, this invention provides a compound offormula I where R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl.

In another generic embodiment, this invention provides a compound offormula I where R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- orsix-membered ring or a 9-14-membered fused ring system, wherein eachring optionally contains 1-3 heteroatoms selected independently from O,N, and S; wherein each ring is optionally substituted with 1-3 groupsselected independently from the following: halogen, hydroxy, cyano, oxo,and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionallysubstituted with one to three halogen atoms; and wherein each ringoptionally contains one or more double bonds.

In still another generic embodiment, this invention provides a compoundof formula I where R′ is CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl.

In one subgeneric embodiment, this invention provides a compound offormula II

in which A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, C(O)CH₂, —S—, or —C(O)—;

-   R₁, R₂, and R₃ are, independently, hydrogen; halogen; hydroxy;    nitro; cyano; C₁-C₄ alkyl, optionally substituted with one to three    fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O);    CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are,    independently, H, CH₃, or CH₃CH₂; or R₁ and R₂ are attached to    adjacent carbons and, together with the ring atoms to which they are    attached, form an additional, fused, five- or six-membered ring,    optionally containing one heteroatom, which ring may be aromatic or    aliphatic;-   R₄-R₆ are, independently, H, F, Cl, Br, CH₃, or CF₃;-   R* is H, except when R₁ and R₂ are both F; when R₁ and R₂ are both    F, R* is either H or Cl;-   R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups    optionally substituted with one to three groups selected    independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B    or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉    bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,    tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl,    where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,    piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups are    optionally substituted with one to three groups selected    independently from hydroxy, halogen, and methyl;-   or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- or    six-membered ring or a 9-14-membered fused ring system, wherein each    ring optionally contains 1-3 heteroatoms selected independently from    O, N, and S; wherein each ring is optionally substituted with 1-3    groups selected independently from the following: halogen, hydroxy,    cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is    optionally substituted with one to three halogen atoms; and wherein    each ring optionally contains one or more double bonds;-   or R′ is —CH(CH₂OH)CH₂D, where D is selected from imidazolyl,    indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, and    adamantin-1-yl.

In another subgeneric embodiment, this invention provides a compound offormula II in which A is O.

In a more specific embodiment, this invention provides a compound offormula II in which A is O and R′ is —CH(CH₂OH)CH₂D, where D is selectedfrom imidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl.

In another embodiment, this invention provides a compound of formula IIin which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is afive- or six-membered ring or a 9-14-membered fused ring system, whereineach ring optionally contains 1-3 heteroatoms selected independentlyfrom O, N, and S; wherein each ring is optionally substituted with 1-3groups selected independently from the following: halogen, hydroxy,cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group isoptionally substituted with one to three halogen atoms; and wherein eachring optionally contains one or more double bonds.

In another embodiment, this invention provides a compound of formula IIin which A is O and R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or—CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl,pyridyl, piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, andnaphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl,bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,tetrahydrofuryl, and naphthyl groups are optionally substituted with oneto three groups selected independently from hydroxy, halogen, andmethyl.

In another subgeneric embodiment, this invention provides a compound offormula II in which A is —O—, R₁ is 2-C(O)G, where G is selected from:

-   —OJ, where J is isopropyl, cyclopropyl, cyclopentyl, dimethylamino,    or methoxyethyl; and-   —NHJ′ where J′ is methyl, ethyl, isopropyl, cyclopropyl,    dimethylaminomethyl, or 3-methyl-2-yl-butanoic acid methyl ester and    —N(CH₃)₂; or N-methyl piperazinyl;-   R₂ and R₃ are H; and R₄ is isopropyl or 1-hydroxy-isopropyl.

In another embodiment, this invention provides a compound of formula IIin which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂;3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH, and R₃ is hydrogen; halogen;hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one tothree fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O);CH₃CH₂OC(O); NR₇R₈; —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are,independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me,5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano;C₁-C₄ alkyl, optionally substituted with one to three fluorine atoms;CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈,—C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃,or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈, and R₃ ishydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionallysubstituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl;(CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, whereR₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is O and R′ is (CH₂)_(n)-G; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃,3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH; and R₃ ishydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionallysubstituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl;(CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, whereR₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is afive- or six-membered ring or a 9- to 14-membered fused ring system,wherein each ring optionally contains 1-3 heteroatoms selectedindependently from O, N, and S; wherein each ring is optionallysubstituted with 1-3 groups selected independently from the following:halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkylgroup is optionally substituted with one to three halogen atoms; andwherein each ring optionally contains one or more double bonds; R₁ is2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; andR₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionallysubstituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl;(CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, whereR₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is O, R′ is (CH₂)_(n)-G; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or—S(O)₂NR₇R₈; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄alkyl, optionally substituted with one to three fluorine atoms; CH₃O;2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or—S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is H;R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe,4-Cl, or 4-OH; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄alkyl, optionally substituted with one to three fluorine atoms; CH₃O;2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or—S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is2-Me, 2-F, or 2-Cl; R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; andR₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionallysubstituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl;(CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, whereR₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is5-Cl; R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈; and R₃ is hydrogen; halogen;hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one tothree fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O);CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R are,independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIin which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is H; R₂ is 2-Cl, 2-Me, 2-CF₃,3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH; and R₃ ishydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄ alkyl, optionallysubstituted with one to three fluorine atoms; CH₃O; 2-methoxy ethenyl;(CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, whereR₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIII in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is 2-Me, 2-F, or 2-Cl; R₂ is 3-Me,3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃; and R₃ is hydrogen; halogen;hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one tothree fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O);CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are,independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula IIII in which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is 5-Cl; R₂ is —C(O)NR₇R₈, or—S(O)₂NR₇R₈; and R₃ is hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄alkyl, optionally substituted with one to three fluorine atoms; CH₃O;2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or—S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂.

In another embodiment, this invention provides a compound of formula III

wherein A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, —C(O)CH₂—, —S—, or —C(O)—; andsubstituents R¹-R′ are as defined for formula I.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—.

In another embodiment, this invention provides a compound of formula IIIin which A is C(O), —CH₂—, or C(O)CH₂.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, and R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all suchC₁-C₆ alkyl and C₃₋₆ cycloalkyl optionally substituted with one to threeOH groups.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; and R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl,N-morpholyl, tetrahydrofuryl, and naphthyl.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; and R′ is 2-propyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OHgroups; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl,N-morpholyl, tetrahydrofuryl, and naphthyl; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl; and R₄ is H, CH₃, or CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OHgroups; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula IIIin which A is —O; R′ is —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₆cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl,N-morpholyl, tetrahydrofuryl, and naphthyl; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl; and R₄ is F, Cl, or Br.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OHgroups; R₄ is H, CH₃, or CF₃; and R₅ is F.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl,N-morpholyl, tetrahydrofuryl, and naphthyl; 4 is H, CH₃, or CF₃; and R₅is F.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl; R₄ is H, CH₃, or CF₃; and R₅ isF.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is C₁-C₆ alkyl or C₃₋₆ cycloalkyl, all such C₁-C₆alkyl and C₃₋₆ cycloalkyl optionally substituted with one to three OHgroups; R₄ is F, Cl, or Br; and R₅ is F.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—; R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₆ cycloalkyl, phenyl, pyridyl, piperazin-1-yl, piperidin-1-yl,N-morpholyl, tetrahydrofuryl, and naphthyl; R₄ is F, Cl, or Br; and R₅is F.

x14 In another embodiment, this invention provides a compound of formulaIII in which A is —O—; R′ is 2-propyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl; R₄ is F, Cl, orBr; and R₅ is F.

x14 sub: In another embodiment, this invention provides a compound offormula III in which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is H, and R₂is selected from 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt,3-C(O)OMe, 4-Cl, and 4-OH.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is H, and R₂ is 2-Cl, 2-Me,2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂, 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 2-Me, 2-F, or 2-Cl; andR₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 5-Cl; and R₂ is—C(O)NR₇R₈, or —S(O)₂NR₇R₈.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 2-Me, 2-F, or 2-C₁ and R₂is 4-F, 4-Cl, 4-1,4-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R₁ is 3-Me or 3-F and R₂ is5-F, 5-Me or 5-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is 2-propyl, 1-hydroxy-2-propyl, 2-hydroxyethyl,3-hydroxypropyl, or 2,3-dihydroxypropyl, R_(1,2) are 2-Cl and 5-Cl,R_(4,5) are 2-F and 5-F, and R₆ is H.

In another embodiment, this invention provides a compound of formula IIIin which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl,5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is O; R′ is —CH(CH₂OH)CH₂D, where D is selected fromimidazolyl, indolyl, carboxamido, phenyl, cyclohexyl, —CH₂SCH₃, andadamantin-1-yl; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈,

In another embodiment, this invention provides a compound of formula IIIin which A is O; R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five-or six-membered ring or a 9-14-membered fused ring system, wherein eachring optionally contains 1-3 heteroatoms selected independently from O,N, and S; wherein each ring is optionally substituted with 1-3 groupsselected independently from the following: halogen, hydroxy, cyano, oxo,and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionallysubstituted with one to three halogen atoms; and wherein each ringoptionally contains one or more double bonds; R₁ is H; and R₂ is 2-Cl,2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula IIIin which A is O and R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is afive- or six-membered ring or a 9-14-membered fused ring system, whereineach ring optionally contains 1-3 heteroatoms selected independentlyfrom O, N, and S; wherein each ring is optionally substituted with 1-3groups selected independently from the following: halogen, hydroxy,cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group isoptionally substituted with one to three halogen atoms; and wherein eachring optionally contains one or more double bonds; R₁ is 2-Me, 2-F, or2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is O, R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five-or six-membered ring or a 9-14-membered fused ring system, wherein eachring optionally contains 1-3 heteroatoms selected independently from O,N, and S; wherein each ring is optionally substituted with 1-3 groupsselected independently from the following: halogen, hydroxy, cyano, oxo,and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionallysubstituted with one to three halogen atoms; and wherein each ringoptionally contains one or more double bonds; R₁ is 5-Cl; and R₂ is—C(O)NR₇R₈, or —S(O)₂NR₇R₈,

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is Hand R₂ is 2-Cl, 2-Me, 2-CF₃, 3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe,4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is2-Me, 2-F, or 2-Cl; and R₂ is 3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is OH; O—C₁-C₆ alkyl; or C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; R₁ is5-Cl; and R₂ is —C(O)NR₇R₈, or —S(O)₂NR₇R₈.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is H; and R₂ is 2-Cl, 2-Me, 2-CF₃,3-F, 3-Me, 3-N(CH₃)₂; 3-C(O)OEt, 3-C(O)OMe, 4-Cl, or 4-OH.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is 2-Me, 2-F, or 2-Cl; and R₂ is3-Me, 3-F, 3-Cl, 5-Me, 5-F, 5-Cl or 3-CF₃.

In another embodiment, this invention provides a compound of formula IIIin which A is —O—, R′ is —CH₂B or —CH₂CH₂B, where B is selected fromC₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉bicycloalkyl, where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl,piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl groups areoptionally substituted with one to three groups selected independentlyfrom hydroxy, halogen, and methyl; R₁ is 5-Cl; and R₂ is —C(O)NR₇R₈, or—S(O)₂NR₇R₈

In another embodiment, this invention provides a compound of formula IV

wherein U, V, W, X, Y, and Z are, independently CH or N, provided thatU, V, W, X, Y, and Z are not all CH; A is —O—, —CH₂—, —N₂—, —NHC(O)—,—CH₂C(O)—, —C(O)CH₂—, —S—, or —C(O)—; R₁ and R₂ are, independently,hydrogen; halogen; hydroxy; cyano; CH₃, optionally substituted with 1-3fluorine atoms; CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; andCH₃CH₂OC(O); and R′ is OH; OC₁-C₆ alkyl; C₁-C₆ alkyl, optionallysubstituted with one to three groups selected independently fromhydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where Bis selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl,piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl;C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl,bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,tetrahydrofuryl, and naphthyl groups are optionally substituted with oneto three groups selected independently from hydroxy, halogen, andmethyl.

In a more specific embodiment, this invention provides a compound offormula IV, in which A is —O—, —CH₂—, —NHC(O)—, —S—, or —C(O)—.

In another embodiment, this invention provides a compound of formula V

wherein U and X are, independently CH or N, provided that U and X arenot both CH; R₁ and R₂ are, independently, hydrogen; halogen; hydroxy;cyano; CH₃, optionally substituted with 1-3 fluorine atoms; CH₃O;(CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ isselected from C₁-C₆ alkyl, optionally substituted with 1-3 hydroxylgroups; cyclopropyl; —CH₂B; and —CH₂CH₂B, where B is selected from C₃₋₆cycloalkyl, phenyl, pyridyl, piperzin-1-yl, piperidin-1-yl, N-morpholyl,tetrahydrofuryl, and naphthyl.

In still another embodiment, this invention provides a compound offormula VI

where Y is —NH—, —S— or —O—, and R₁—R′ are defined as for formula II.

In a more specific embodiment, this invention provides a compound offormula VIa, where Y is —NH—, —S— or —O—,

In a more specific embodiment, this invention provides a compound offormula VIa where Y is —S— or —O—, and R′ is selected from1-hydroxy-isopropyl, 2-hydroxy-n-propyl, 2-hydroxy-ethyl, and2,3,-dihydroxy-n-propyl.

In another generic embodiment, this invention provides a compound offormula VII

where the dashed bond represents an optional double bond, and wheresymbols T-Z represent N, CH, or CR_(1, 2, or 4), provided that at mosttwo of W, X, Y, and Z and at most 2 of T, U, and V are N; where R₁-R₄are defined as for formula I; and where R′ is OH; O—C₁-C₆ alkyl; C₁-C₆alkyl, said C₁-C₆ alkyl groups optionally substituted with one to threegroups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, andphenyl; or R′ is —(CH₂)_(n)—B where n is 1 or 2 and B is defined asabove.

In one subgeneric embodiment, this invention provides a compound offormula VIIa,

where R₁-R₄ and R′ are defined as for formula I.

In a more specific embodiment, this invention provides a compound offormula VIIa where R₁ is defined as in formula II, R₃ and R₄ are both Hand R′ is —(CH₂)_(n)—B, where n is 1 or 2 and B is defined as above.

In another more specific embodiment, this invention provides a compoundof formula VIIa where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl orO—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compoundof formula VIIa, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIa, where R₂—R are H and R′ is —(CH₂)_(n)—B, where n is 1or 2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl,oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl,3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In another subgeneric embodiment, this invention provides a compound offormula VIIA in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIA in which R₁ is 2-fluoro, -chloro, -bromo,-methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates thecompound of formula VIIA in which R₁ is 3-fluoro, -chloro, -bromo,-methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates thecompound of formula VIIA in which R₁ is 4-fluoro, -chloro, -bromo,-methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a another more specific embodiment, this invention contemplates thecompound of formula VIIA in which R₁ is 5-fluoro, -chloro, -bromo,-methyl, -trifluoromethyl, -methoxy, or -hydroxy; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In another subgeneric embodiment, this invention provides a compound offormula VIIA-1, where R₁—R′ are defined as for formula A.

In a more specific embodiment, this invention provides a compound offormula VIIA-1 where R₁-R₄ are H and R′ is isopropyl, 2-butyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another generic embodiment, this invention provides a compound offormula VII, in which at least one of T, U, V, W, X, Y, and Z is N.

In another generic embodiment, this invention provides a compound offormula VII, in which at least one of W, X, Y, and Z is N.

In another generic embodiment, this invention provides a compound offormula VII, in which at least one of T, U, and V is N.

In another generic embodiment, this invention provides a compound offormula VII, in which two of W, X, Y, and Z are N.

In another generic embodiment, this invention provides a compound offormula VII, in which one of T, U, and V and one of W, X, Y, and Z areN.

In another generic embodiment, this invention provides a compound offormula VIIB

where substituents are defined as for formula II.

In a subgeneric embodiment, this invention provides a compound offormula VIIB-1

In a more specific embodiment, this invention provides a compound offormula VIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, orhalogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, where R₁-R₄ are H and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1 where one of R₁ and R₂ is H and the other is amino,methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, where one of R₁ and R₂ is H and the other is nitro,cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are Hand R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound offormula VIIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-1, where R₁ is halo, R₂-R₄ are H and R′ is —(CH₂)_(n)—B,where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, the invention contemplates acompound of formula VIIB-1, where R₁ is bromo, R₂-R₄ are H and R′ isisopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or2,3-dihydroxy-1-propyl.

In a subgeneric embodiment, this invention provides a compound offormula VIIB-2

In a more specific embodiment, this invention provides a compound offormula VIIB-2, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, orhalogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In another more specific embodiment, this invention provides a compoundof formula VIIB-2, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, the invention contemplates acompound of formula VIIB-2, where R₁ is bromo, R₂-R₄ are H and R′ is2-cyclopropyl ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or2,3-dihydroxy-1-propyl.

In another more specific embodiment, the invention contemplates acompound of formula VIIB-2, where R₁ and R₂ are fused (2,3) pyrido, R₄is 2-chloroethyl, and R′ is 2-cyclopropyl ethyl, 2-hydroxyethyl, or2-cyclopenylethyl.

In another more specific embodiment, the invention contemplates acompound of formula VIIB-2, where R₁ and R₂ are fused (2,3) pyrrolo,fused (2,3) furyl, or fused (4,5) imidazolo, R₄ is H, and R′ is2-hydroxyethyl, or isopropyl.

Additional embodiments of generic structures with one or more ofT-Z=nitrogen are shown below, together with a contemplated compound foreach generic structure. These contemplated compounds indicate the rangeof contemplated substituents.

Generic Structure Example

VIIB-3 VIIB-3a

VIIB-4 VIIB-4a

VIIB-5 VIIB-5a

VIIB-6 VIIB-6a

VIIB-7 VIIB-7a

VIIB-8 VIIB-8a

VIIB-9 VIIB-9a

VIIB-10 VIIB-10a

VIIB-11 VIIB-11a

VIIB-12 VIIB-12a

VIIB-13 VIIB-13a

VIIB-14 VIIB-14a

VIIB-15 VIIB-15a

VIIB-16 VIIB-16a

VIIB-17 VIIB-17a

VIIB-18 VIIB-18a

VIIB-19 VIIB-19a

VIIB-20 VIIB-20a

VIIB-21 VIIB-21a

VIIB-22 VIIB-22a

VIIB-23 VIIB-23a

VIIB-24 VIIB-24a

VIIB-25 VIIB-25a

VIIB-26 VIIB-26a

VIIB-27 VIIB-27a

VIIB-28 VIIB-28a

VIIB-29 VIIB-29a

VIIB-30 VIIB-30a

VIIB-31 VIIB-31a

VIIB-32 VIIB-32a

VIIB-33 VIIB-33a

VIIB-34 VIIB-34a

VIIB-35 VIIB-35a

VIIB-36 VIIB-36a

VIIB-37 VIIB-37a

In additional embodiments, the invention provides compounds according toany of formulas VIIB-3 to VIIB-37, wherein R₁-R₄ are all independentlymethyl, methoxy, ethyl, vinyl, ethynyl, halo, or H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl, cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention providescompounds according to any of formulas VIIB-3 to VIIB-37, wherein R₁-R₄are all independently halo, halomethyl, or H, and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl, piperazinonyl,piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, orpyrimidyl.

In additional more specific embodiments, the invention providescompounds according to any of formulas VIIB-3 to VIIB-37, wherein R₁-R₄are all independently halo, halomethyl, or H, and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is quinolyl, thiazolidinonyl,isothiazolidinonyl, or oxindolyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIB-3 to VIIB-37, where R₁ isbromo, R₂-R₄ are H, and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIB-3 to VIIB-37, where R₁-R₄are H and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIB-3 to VIIB-37, where R₁ ispropyn-3-yl, R₂-R₄ are H and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIB-3 to VIIB-37, where R₁ isnitro or cyano, R₂-R₄ are H and R′ is 2-hydroxyethyl or 2-hydroxypropyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIB-3 to VIIB-37, where R₂ isdimethylamino or dimethylaminomethyl, R₁, R₃, and R₄ are H and R′ isisobutyl or 3-cyclopentyl-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIB-3 to VIIB-37, where R₁-R₃ are H, R₄ ischloro, and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIB-3 to VIIB-37, where R₂ is bromo, R₁,R₃, and R₄ are H, and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

Additional contemplated compounds for generic embodiments of formula VIIare shown in the tables below.

Cpd Structure 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

In another generic embodiment, this invention provides a compound offormula VIII below,

where the dashed bond represents an optional double bond, where symbolsW-Z represent N, CH, or CR_(1 or 2), and where R₁-R′ are, defined as forformula VII.

In one subgeneric embodiment, this invention provides a compound offormula VIIIA below,

where the dashed bond represents an optional double bond, and where allsubstituents are defined as for formula VIII.

In another generic embodiment, this invention provides a compound offormula VIIIB,

where the dashed bond represents an optional double bond, where allsubstituents are defined as for formula VIII, and where symbols W-Zrepresent N, CH, or CR_(1 or 2), provided that at least one of W-Z is N.

In one subgeneric embodiment, this invention provides a compound offormula VIIIA-1,

where all substituents are defined as for formula VIII.

In a more specific embodiment, this invention provides a compound offormula VIIIA-1, where R₁ and R₂ are as described above for formulaVIII; R₃ and R₄ are both H; and R′ is —(CH₂)_(n)—B, where n is 1 or 2and B is a five- or six-membered ring or a 9- to 14-member fused ringsystem, wherein each ring optionally contains 1-3 heteroatoms selectedindependently from O, N, and S; wherein each ring is optionallysubstituted with 1-3 groups selected independently from the following:halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkylgroup is optionally substituted with one to three halogen atoms; andwherein each ring optionally contains one or more double bonds.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are as described above; R₃ and R₄are both H; and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionallysubstituted as described above.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are as described above; R₃ and R₄are both H and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionallysubstituted as described above.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁-R₄ are H and R′ is C₁-C₆ alkyl or O—C₁-C₆alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; andR′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is halogen; R₂-R₄ are H; and R′ ismethyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; andR′ is 1,2-chloropropan-3-yl or 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is bromo; R₂-R₄ are H; and R′ isisopropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are H; andR′ is 1,2-dihydroxy-propan-3-yl, 2-hydroxyethyl,1,2-dihydroxybutan-4-yl, or 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are C₁-C₆alkyl; and R′ is 1,2-dihydroxybutan-3-yl or 4-methoxybutyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are 5-chloro and 6-chloro; R₃ andR₄ are H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are H; R₃ is 2-hydroxy; R₄ is H;and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are 5-chloro and 6-chloro; R₃ is2-hydroxy; R₄ is H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen;R₃ is H, 2-OH, or 2-methyl; R₄ is H or methyl; and R′ is1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are halogen; R₃ and R₄ are,independently H, OH, or methyl; and R′ is 1-hydroxy-butan-3-yl,1,2-dihydroxy-propan-3-yl, or 2-hydroxyethyl

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is halo; R₂-R₄ are, independently H, OH,or methyl; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen;R₃ and R₄ are, independently, H, OH, or methyl; and R′ is 4-hydroxybutylor 1,2-dihydroxybutan-4-yl

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are, independently, H or halogen;R₃ and R₄ are, independently, H, OH, or methyl; and R′ is1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are, independently, H, C₁-C₆alkyl, C₁-C₆ alkenyl, C₁-C₆ cycloalkyl, or halogen; R₃ and R₄ are,independently, H, OH, or C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are, independently, H, C₁-C₆alkyl, or halogen; R₃ and R₄ are, independently, H, OH or methyl; and R′is 4-methoxybutyl, 3-hydroxypropyl or 2-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl; R₃ and R₄ are, independently, H, OH, or methyl; and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are benzo; R₃ and R₄ are,independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 4 and 5, arefused (4,5)-imidazolo; R₃ and R₄ are, independently, H, OH, or methyl;and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, arefused (2,3)-furyl, (2,3)-pyridyl, or fused cyclopentyl; R₃ and R₄ are,independently, H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, arefused cyclopentyl; R₃ and R₄ are, independently, H, OH, or methyl; andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 6 and 7, arefused cyclopentyl, R₃ and R₄ are, independently, H, OH, or methyl; andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 5 and 6, arebenzo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 6 and 7, arebenzo; R₃ and R₄ are, independently, H, OH, or methyl; and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-1, where R₁ and R₂, at positions 4 and 5, arebenzo, said benzo group bearing fluoro at each ortho position; R₃ and R₄are, independently, H, OH, or methyl; and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁-R₄ are H and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two hydroxy groups.

In another still more specific embodiment, this invention provides acompound of formula VIIIA-1, where R₁, R₂, and R₄ are H; R₃ is methyl orOH; and R′ is C₁-C₄ alkyl, optionally substituted with one or twohydroxy groups.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ isH, OH, or C₁-C₄ alkyl, optionally substituted with halogen or hydroxy;and R′ is C₁-C₄ alkyl, optionally substituted with one or two hydroxygroups.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ ismethyl, optionally substituted with halogen or hydroxy; and R′ is C₁-C₄alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ isC₁-C₄ alkyl, optionally substituted with halogen or hydroxy; and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl,thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ andR₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 6-chloro, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 7-chloro, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 7-bromo, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ areH, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-1, in which R₁ is 5-CF₃, R₂, R₃, and R₄ are H,and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are bothhalogen, R₃ is 2-chloromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is 2-pyridyl, 3-pyridyl, 4-pyridyl,2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are bothhalogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or3-morpholyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ and R₂, in positions 4 and 6, are bothhalogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B,where n is 2, and B is 4-bromo-2-pyrimidyl, 2-chloro-4-pyrimidyl,2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-1, in which R₁ is 3-hydroxy, 5-dimethylamino,4-methoxy, 5-(2-methoxyethyl), or 6-methoxymethyl R₂-R₄ are H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-1, in which R₁ is 4-ethoxy, 4-cyano, 4-CH₂F,7-acetoxy, 7-acetyl, 6-methyloxycarbonyl, 6-dimethylaminocarbonyl,4-dimethylamino, 5-dimethylaminocarbonyl, 5-methyloxycarbonyl, 4-acetyl,4-acetoxy, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or2, and B is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl,oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another embodiment, this invention provides a compound of formulaVIIIA-2

In a more specific embodiment, this invention provides a compound offormula A-2, where R₃ and R₄ are both H and R′ is —(CH₂)_(n)—B.

In another subgeneric embodiment, this invention provides a compound offormula VIIIA-2, where R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, bothoptionally substituted as described above.

In another subgeneric embodiment, this invention provides a compound offormula VIIIA-2, where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl orO—C₁-C₆ alkyl, both optionally substituted as described above.

In a more specific embodiment, this invention provides a compound offormula VIIIA-2, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another still more specific embodiment, this invention provides acompound of formula A-1, where R₁, R₂, and R₄ are H; R₃ is H, methyl orOH; and R′ is C₁-C₄ alkyl, optionally substituted with one or twohydroxy groups.

In another more specific embodiment, this invention provides a compoundof formula A-1, where R₁ and R₂ are H; R₃ is H, methyl, or OH; R₄ isC₁-C₄ alkyl, optionally substituted with halogen or hydroxy; and R′ isC₁-C₄ alkyl, optionally substituted with one or two hydroxy groups.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, where R₁, in position 5, is dimethylamino,dimethylaminomethyl, or acetylamino, R₃, in position 3, is methoxy ormethoxymethyl, R₂ and R₄ are H, and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, where R₁, in position 4, is dimethylamino,dimethylaminomethyl, or acetylamino, R₂, in position 6, is bromomethyl,R₃ and R₄ are H, and R′ is mono-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, in which R₁ and R₂, in positions 4 and 6, are bothhalogen, R₃ is 2-chloromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B,where n is 1, and B is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl,3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIA-2, in which R₁ and R₂, in positions 4 and 6, are bothhalogen, R₃ is 3-fluoromethyl, and R₄ is H, and R′ is —(CH₂)_(n)—B,where n is 1, and B is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or3-morpholyl.

In a more specific embodiment, this invention contemplates a compound offormula VIIIA-2, where R₁-R₄ are H and R′ is 2-(2-furyl)ethyl,2-hydroxyethyl, or 2,3-dihydroxy-1-propyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ and R₂ together, at positions 5and 6, are benzo or fused cyclopentyl, R₃ and R₄ are H, and R′ isisopropyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ and R₂ together, at positions 6and 7, are fused 2,3-pyrido or pyrrolo, R₃ and R₄ are H, and R′ isisopropyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ and R₂ together, at positions 4and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ and R₂ together, at positions 6and 7, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is2-hydroxyethyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-2 in which R₁ and R₂ are both H, R₃ is 4-methyl or5-methyl, R₄ is 7-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, andB is pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-2 in which R₁ is 4-CF₃, R₃ is 6-hydroxymethyl, R₂ andR₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-2 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-2 in which R₁ is 5-chloro, 6-chloro, or7-chloro, R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-2 in which R₁ is 3-bromo, 4-bromo, or 5-bromo,R₂, R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and Bis pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula VIIIA-2 in which R₁ is 6-chloro, R₂ is 7-chloro, R₃and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-2 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ is 4-CF₃, R₂, R₃, and R₄ are H,and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula VIIIA-2 in which R₁ is 4-cyano, 4-hydroxy, 4-methoxy,5-hydroxy, or 4-methoxymethyl, R₂-R₄ are H, and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ is 4-dimethylamino, 7-acetyl,7-dimethylamino, 7-dimethylaminocarbonyl, or 7-methyloxycarbonyl, R₂,R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B isisothiazol-4-yl, isoxazol-3-yl, oxazol-2-yl, 2-oxazolin-2-yl,oxazolidin-4-yl, thiazol-2-yl, thien-2-yl, fur-2-yl, pyrrol-3-yl,pyrrolin-4-yl, pyrrolidin-3-yl, thiazolin-4-yl, thiazolidin-4-yl,imidazol-2-yl, 2-pyridyl, 4-pyridyl, m-tolyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ is 6-acetoxy, or 7-acetoxy, R₂,R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ is 7-acetyl, or 7-acetoxy, R₂,R₃, and R₄ are H, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula VIIIA-2 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H,and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

The following are subgeneric embodiments, as well as more specificembodiments and prophetic examples, which contain one or more ofW-Z=nitrogen.

In one subgeneric embodiment, this invention provides a compound offormula VIIIB-1,

where all substituents are defined as for formula VIIIA.

In a more specific embodiment, this invention provides a compound offormula VIIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, OH, orhalogen; and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, OH,or halogen; and R′ is C₁-C₄ alkyl, optionally substituted with one ortwo hydroxy groups.

In a still more specific embodiment, this invention provides a compoundof formula VIIIB-1, where R₁-R₄ are H and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a specific contemplated example, this invention provides a compoundof formula VIIIB-1, where R₁-R₄ are H and R′ is 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or isopropyl.

In a specific contemplated example, this invention provides a compoundof formula VIIIB-1, where R₁ and R₂ are H; R₃ is 2-methyl or 2-hydroxy;R₄ is H or methyl; and R′ is isopropyl.

In another specific contemplated example, this invention provides acompound of formula VIIIB-1, where R₁ and R₂ are H; R₃ is 2-methyl or2-hydroxy; R₄ is H or methyl; and R′ is 2,3-dihydroxy-1-propyl or1-hydroxy-2-propyl.

In another specific contemplated example, this invention provides acompound of formula VIIIB-1, where R₁ is C₁-C₄ alkyl, C₁-C₄ alkenyl,C₁-C₄ alkynyl, halomethyl, or halogen; R₂-R₄ are H; and R′ is3,4-dihydroxy-2-butyl.

In another specific contemplated example, this invention provides acompound of formula VIIIB-1, where R₁ is C₁-C₄ alkyl, C₁-C₄ alkenyl,C₁-C₄ alkynyl, halomethyl, or halogen; R₂— is H; R₃ is 2-OH; R₄ ismethyl or H; and R′ is 3,4-dihydroxy-2-butyl.

In another specific contemplated example, this invention provides acompound of formula VIIIB-1, where R₁-R₄ are H and R′ is3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula VIIIB-1, where R₁-R₄ are H and R′ is ethoxy,isopropoxy, or O—CH(CH₃)CH₂CH₃.

In another specific contemplated example, this invention provides acompound of formula VIIIB-1, where R₁-R₄ are H and R′ is ethoxy.

In another more specific embodiment, this invention contemplates acompound of formula VIIIB-1, where R₁-R₄ are H and R′ is 2-chloroethyl,2-bromoethyl, or 1,2-dichloro-3-propyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1 where one of R₁ and R₂ is H and the other is amino,methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, where one of R₁ and R₂ is H and the other is nitro,cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are Hand R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl,or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, wherein R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound offormula VIIIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-1, where R₁ is halo, R₂-R₄ are H and R′ is—(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, the invention contemplates acompound of formula VIIIB-1, where R₁ is bromo, R₂-R₄ are H and R′ isisopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or2,3-dihydroxy-1-propyl.

In another embodiment, this invention provides a compound of formulaVIIIB-2,

where substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound offormula VIIIB-2, where R₁-R₄ are, independently, H or halogen, and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2-methoxyethyl,1-hydroxy-2-propyl,1,2-dihydroxy-3-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-2, where one of R₁ and R₂ is H and the other is amino,methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula VIIIB-2, where one of R₁ and R₂ is H and the other is nitro,cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are Hand R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

Additional subgeneric embodiments of compounds of formula I with one ormore of W-Z=nitrogen are shown below.

In more specific embodiments, the invention provides compounds accordingto any of formulas VIIIB-3 to VIIIB-20, wherein R₁-R₄ are allindependently methyl, methoxy, ethyl, vinyl, ethynyl, halo, OH, or H,and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention providescompounds according to any of formulas VIIIB-1 to VIIIB-20, whereinR₁-R₄ are all independently halo, halomethyl, OH, or H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas VIIIB-1 to VIIIB-20, where R₁ isbromo; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are,independently, H, OH, C₁-C₄ alkyl, C₁-C₄ alkenyl, C₁-C₄ alkynyl, halo,halomethyl, nitro, or cyano; and R′ is isopropyl or2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are all Hand R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₄ are H; R₃and R₄ are, independently, H, methyl, or OH; and R′ is isopropyl or2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁ is acetyl,acetoxy, acetamido, methylcarbamoyl, methylsulfonyl, methyloxycarbonyl,ethyloxycarbonyl, or cyclopropylethynyl; R₂-R₄ are all H; and R′ isisopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁ is acetyl,acetoxy, acetamido, methylcarbamoyl, methylsulfonyl, methyloxycarbonyl,ethyloxycarbonyl, or cyclopropylethynyl; R₂ is H; R₃ is 2-OH or2-methyl; R₄ is H, OH, or methyl; and R′ is isopropyl or2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₁-R₃ are all H;R₄ is chloro; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas VIIIB-1 to VIIIB-20, where R₂ is bromo; R₁,R₃, and R₄ are all H; and R′ is isopropyl or 2,3-dihydroxy-1-propyl.

A number of prophetic examples of compounds according to formulasVIIIB-1 to VIIIB-20 are shown below.

Still more prophetic examples of compounds of this invention are shownbelow:

In another generic embodiment, this invention provides a compound offormula IX,

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), providedthat no two nitrogen atoms are adjacent, where R₁-R₄ are, defined as forformula I.

In one subgeneric embodiment, this invention provides a compound offormula A below, where all substituents are as defined for formula Iabove.

In another embodiment, this invention provides a compound of formulaIXB,

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), providedthat at least one of M, Q, T, U, and V is N, and further provided thatno two nitrogen atoms are adjacent, and where R₁-R₄ are as defined asabove.

In one more specific embodiment, this invention provides a compound offormula IXA, where R₁-R₄ are defined as for formula IX, and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl,isoxazolindinonyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, thiazolidinonyl, isothiazolinyl,isothiazolidinyl, isothiazolidinonyl, imidazolinyl, imidazolyl, pyridyl,tolyl, or phenyl, wherein all rings are optionally substituted asdescribed above.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ and R₂ are as defined for formula IX; R₃ and R₄are both H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R is 2-chloro, R₂ is 6-methyl, and R₃—R′ are asdefined for formula IXA.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₄ are defined as for formula I, and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is naphthyl, quinolyl,isoquinolyl, indanyl, or benzimidazolyl, wherein all rings areoptionally substituted as described above in the definition of G forformula I.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₄ are defined as for formula I, and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is cyclopentyl, cyclohexyl,tetrahydrofuryl, tetrahydrothienyl, piperidyl, piperazinyl, ormorpholyl, wherein all rings are optionally substituted as with methylor halo.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₄ are defined as for formula I, and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, 2-pyrrolidon-1-yl, or2-pyrrolidon-6-yl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₃ are as defined for formula I, R₄ is H ormethyl, and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In a still more specific and more preferred embodiment, this inventionprovides a compound of formula IXA, where R₁ and R₂, in positions 2 and6, are alkyl or halo, R₃ is H, R₄ is H or methyl, and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₄ are defined as for formula II, and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, where R₁-R₃ are as defined for formula II, R₄ is H ormethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific and more preferred embodiment, this inventionprovides a compound of formula IXA, where R₁ and R₂, in positions 2 and6, are alkyl or halo, R₃ is alkyl, haloalkyl, cycloalkyl, alkenyl, oralkynyl, R₄ is H or methyl, and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific and more preferred embodiment, this inventionprovides a compound of formula IXA, where R₁ and R₂, in positions 2 and6, are alkyl or halo, R₃ is H, R₄ is H or methyl, and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, where R₁ and R₂ are, independently, H, halo, or C₁-C₃alkyl; R₃ and R₄ are both H; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a preferred and more specific embodiment, this invention provides acompound of formula IXA, in which R₁ is 2-halo or 2-methyl; R₂ is6-methyl; R₃ and R₄ are, independently, H, C₁-C₃ alkyl, or halo; and R′is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃ andR₄ are, independently, H, C₁-C₃ alkyl, vinyl, cyclopropyl, or halo; andR′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula IXA, in which R₁ is 2-methyl; R₂ and R₃ are H; R₄ ismethyl; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula IXA, in which R₁-R₄ are H; and R′ is isopropyl ormono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred subgeneric embodiment, this invention providesa compound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃and R₄ are, independently, H, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ alkenyl,C₁-C₃ alkenoxy, hydroxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 1or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a more specific embodiment, this invention provides a compound offormula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃ and R₄ are,independently, H, methyl, methoxy, vinyl, 2-methoxyethene, hydroxy, orchloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ is C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆cycloalkyl; R₂ and R₃ are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, where R₁ is 2-methylpropenyl, 1-propynyl, orcyclopropyl; R₂ and R₃ are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetamido; R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl; R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂-R₄are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-methyl; R₂ and R₃ are both halogen; R₄is H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are both chloro; R₃ is H; R₄ ismethyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, ortetrahydro furyl, or R′ is C₁-C₆ alkyl, optionally substituted with oneor two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-methyl; R₂ and R₃ are both H; R₄ is2-chloroethyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-hydroxymethyl; R₃ is 4-CF₃; R₂ and R₄are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ 3-methyl; R₂ is 5-chloro; R₃ and R₄ are bothH; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another specific embodiment, this invention provides a compound offormula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-isothiazolyl,3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl,3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound offormula IXA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂, R₃,and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl;oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl,thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl,isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl,isoindolyl, quinolyl, isoquinolyl, or naphthyl, or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 3-chloro; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₃;and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 4-chloro; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ and R₂ are 2- and 6-chloro; R₂, R₃,and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-bromo; R₂; R₃; and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 3-bromo; R₂; R₃; and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 4-bromo; R₂, R₃, and R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-, 3-, or 4-bromo; R₂, R₃, andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula IXA, in which R₁ is 4-bromo; R₂ is 2-methyl; R₃ is 3-methyl;R₄ is H, methyl, or halo; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula IXA, in which R₁ is 2-bromo; R₂ is 6-methyl; R₃ is 3-methyl;R₄ is H, methyl, or halo; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula IXA, in which R₁ is 3-bromo; R₂ is 6-methyl; R₃ is H; R₄ isH, methyl, or halo; and R′ is C₁-C₄ alkyl, optionally substituted withone or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-chloro; R₂ is 4-chloro; R₃ andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-methyl; R₂ is 6-methyl; R₃ andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ areH; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-CF₃; R₂; R₃; and R₄ are H; andR′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂, in positions 2 and 6, are,independently, methyl or halogen; R₃ is 2-chloromethyl, R₄ is H; and R′is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl,4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl or R′ is isopropylor mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂, in positions 2 and 6, are,independently, methyl or halogen; R₃ is 3-fluoromethyl; and R₄ is H; R′is —(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyrimidyl, 4-pyrimidyl,2-morpholyl, or 3-morpholyl or R′ is isopropyl or mono- or di-hydroxyC₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂, in positions 2 and 6, are,independently, methyl or halogen; R₃ is 3-methyl; and R₄ is H; R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 2-pyridyl, 3-pyridyl,4-pyridyl, 2-piperidyl, 3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂, in positions 2 and 6, are,independently, methyl or halogen; R₃ is 3-fluoromethyl; and R₄ is H; R′is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-bromo-2-pyrimidyl,2-chloro-4-pyrimidyl, 2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-cyano; R₂ is H or 6-methyl; R₃ and R₄are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-hydroxy; R₂ is H or 6-methyl; R₃ and R₄are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-hydroxy; R₂ is H or 2-methyl; R₃ and R₄are, independently, H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropylor mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or2-methyl; R₃ and R₄ are, independently, H, hydroxy, or methyl; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or6-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-ethoxymethyl; R₂ is H or6-methyl; R₃ and R₄ are, independently, H, hydroxy, or methyl; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxymethyl; R₂ is H or6-methyl; R₃ and R₄ are, independently, H, hydroxy, methoxy, halo, ormethyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-(2-methoxyethyl); R₂ is H, 2-methyl, or6-methyl; R₃ and R₄ are, independently, H, hydroxy, methoxy, or methyl;and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-(2-methoxyethyl); R₂ is H, 2-methyl, or6-methyl; R₃ and R₄ are, independently, H or methyl; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂is H or 6-methyl; R₃ and R₄ are, independently, H, methyl, or hydroxy;and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂is H or 6-methyl; R₃ is 3-methyl; R₄ is methyl, halo, or H; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₃ is H or methyl; R₄ isH; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl;R₂ is H or 6-methyl; R₃ is H or methyl, R₄ is H; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂ is H or6-methyl, R₃ is H, chloro, or methyl; R₄ is H or 5-methyl; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂ is H or6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy,or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3- or4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₃ is H or 3-methyl; R₄ isH, methyl, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted withone or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl;R₂ is H or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy,methoxy, or chloro; and R′ is C₁-C₆ alkyl, optionally substituted withone or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3- or 4-chloroacetyl; R₂ isH or 6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, orchloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3- or 4-acetoxy; R₂ is H or6-methyl; R₃ is H or methyl; R₄ is H, hydroxy, methoxy, or chloro; andR′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3- or 4-fluoromethyl; R₂ isH or 6-methyl; R₃ is H or methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-cyano; R₂ is H or 6-methyl; R₃ is H ormethyl; R₄ is H, methyl, hydroxy, methoxy, halomethyl, or chloro; and R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3- or 4-ethoxy; R₂ is H or 6-methyl;R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, vinyl, halomethyl,or chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-vinyl; R₂ is H or 6-methyl;R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G,where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethylmorpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂ is H or6-methyl; R₃ is H or methyl; R₄ is H, methyl, hydroxy, methoxy, orchloro; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-methoxy; R₂-R₄ are H; R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-methyl; R₂ is 4-methylsulfonyl; R₃ andR₄ are, independently, H, hydroxy, halomethyl, or methyl; and R′ is—(CH₂)_(r)-G, where n is 1, and G is 3-methyl-2-isothiazolyl,3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl,3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or6-methyl; R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is—(CH₂)_(n)-G, where n is 1, and G is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-bromo; R₂ is H or 6-methyl;R₃ is H or methyl; R₄ is H, methyl, or chloro; and R′ is —(CH₂)_(n)-G,where n is 1, and G is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-chloro; R₂ is 3-, 4-, 5-, or6-cyclopropyl, R₃ and R₄ are, independently, H, halo, or methyl; and R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-cyclopropyl; R₂-R₄ are H; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-cyclopropyl; R₂ is 2-, 4-, 5-, or6-chloro; R₃ and R₄ are H; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-chloro; R₂ istrans-4-(2-methylcyclopropyl); R₃ and R₄ are H; R′ is —(CH₂)_(n)-G,where n is 1, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl,oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-cyclopropyl; R₂ is 2- or 3-chloro; R₃and R₄ are, independently, H, halo, or C₁-C₃ alkyl; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-isopropyl; R₂ is 2-chloro; R₃ is 2- or3-chloro; R₄ is methyl, hydroxy, methoxy, or halo; and R′ is—(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are both halogen; R₃ is 3-methyl; R₄is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are both H; R₃ is 3-chloro; R₄ ismethyl, hydroxy, methoxy, or halo; and R′ is —(CH₂)_(n)-G, where n is 2,and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups or R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are both H; R₃ is 2-(2-chloroethyl);R₄ is methyl, hydroxy, methoxy, or halo; R′ is —(CH₂)_(n)-G, where n is2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl, or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-hydroxymethyl; R₂ is 4-CF₃; R₃ and R₄are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3-chloro; R₂ and R₃ are both H; R₄ ismethyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which one or both of R₁ and R₂ are CF₃; R₃ and R₄ areH; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a more specific embodiment, this invention contemplates the compoundof formula IXA, in which R₁ is 4-chloro; R₂ is 3-chloro; R₃ and R₄ areH; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-, 3-, or 4-fluoro; R₂, R₃, andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is fluoro; R₂ is methyl; R₃ and R₄are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 6-chloro; R₂, R₃, and R₄ are H;R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-bromo, 3-bromo, or 4-bromo; R₂is methyl; R₃; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 2-(2-chloroethyl); R₂ is6-chloro; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula IXA, in which R₁ is 4-(3-chloropropyl); R₂ is2-bromomethyl; R₃ and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 2, and Gis pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-CF₃; R₂, R₃, and R₄ are H; R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazol-4-yl,isoxazol-4-yl, oxazol-2-yl, 2-oxazolin-4-yl, oxazolidin-5-yl, orthiazol-2-yl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-cyano; R₂ is 2-methyl; R₃ and R₄ are Hor methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-methyl; R₂ is 4- or 5-hydroxy; R₃ andR₄ are, independently, H, hydroxy, methoxy, halo, or methyl; R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-hydroxymethyl; R₂-R₄ are H; R′ is—(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another specific embodiment, this invention provides a compound offormula IXA, in which R₁ is 2-methoxy; R₂ is H, halo, or methyl; R₃ andR₄ are, independently, H or methyl; R′ is —(CH₂)_(n)-G, where n is 2,and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl, or R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-methoxy; R₂-R₄ are H; R′ is—(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂;R₃; and R₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₃, andR₄ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or twoor hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂, R₃,and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 4-methyloxycarbonyl; R₂ is H ormethyl; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, andG is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₃, andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂; R₃;and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, in which R₁ is 2-, 3-, or 4-CH₂F; R₂; R₃; andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-cyano; R₂-R₄ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-ethoxy; R₂-R₄ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-trifluoromethoxy; R₂-R₄ areH; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂-R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, morpholyl, orimidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₄ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is 5-oxazolidinyl,4-thiazolyl, 3-thienyl, 2-furyl, 3-pyrrolyl, 2-pyrrolidinyl,N-pyrrolidinonyl, N-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3- or 4-methylsulfonyl R₂ is 2-(2-methylcyclopropyl); R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or2, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl,3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl,N-pyrrolidonyl, or m-tolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₄ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 4-bromo or 4-bromomethyl; R₂-R₄ are H;and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2- or 3-chloro; R₂ is4-(2-cyclopropylethyl); R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where nis 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is cyclopropyl or cyclopropylmethyl; R₂-R₄are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is trans-3-(2-methylcyclopropyl); R₂ is6-chloro; R₃ and R₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 3- or 4-cyclopropyl; R₂ is 5-chloro; R₃is 2-(2-fluoroethyl); and R₄ is H, hydroxy, methoxy, or halo; and R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is 2- or 3-cyclopropyl; R₂ is 6-chloro; R₃is 3-chloro; R₄ is methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another embodiment, this invention provides a compound of formulaIXA, in which R₁ and R₂ are halogen or methyl; R₃ and R₄ are H; and R′is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is halogen or methyl; R₂-R₄ are H; and R′ ismethyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ is bromo; R₂-R₄ are H; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are C₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are halogen or methyl; R₃ and R₄ areH; and R′ is 4-methoxybutyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, in which R₁ and R₂ are, independently, halogen ormethyl; R₃ and R₄ are H; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula IXA, where R₁ and R₂ together are fused cyclohexyl or fusedcyclopentyl; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arefused (4,5)-imidazolo; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-Butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arefused (2,3)-furyl; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arefused (2,3)-pyrido; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arefused (3,4)pyrrolyl; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 2 and 3, arefused cyclopentyl; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arefused cyclopentyl; R₃ and R₄ are H; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 2 and 3, arebenzo; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl,2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 2 and 3, arebenzo, substituted at one or both ortho positions; R₃ and R₄ are H; andR′ is isopropyl, (2-tetrahydrofuryl)methyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula IXA, where R₁ and R₂, at positions 3 and 4, arebenzo; R₃ and R₄ are H; and R′ is isopropyl, (2-tetrahydrofuryl)methyl,2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

Specific prophetic examples of compounds of formula IXA are shown below,

Subgeneric embodiments of formula IXB are shown below:

In one subgeneric embodiment, this invention provides a compound of anyof formulas IXB-1-IXB-6, in which R₁, R₂, and R₄ are, independently, H,C₁-C₄ alkyl, alkenyl, alkynyl, cycloalkyl, cyano, acetyl, acetoxy,acetamido, methylcarbamoyl, dimethylamino, or halo; R₃ is H, and R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl, optionally substituted as describedabove, or R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a more specific embodiment, this invention provides a compoundaccording to formula IXB-1, where R₁ is 3-methyl or 3-halo; R₂ and R₃are H; R₄ is H, vinyl, cyano, halo, hydroxy, or methyl; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a more specific embodiment, this invention provides a compoundaccording to formula IXB-1, where R₁ is 3-methyl or 3-halo; R₂ and R₃are H; R₄ is H or methyl; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 2-methyl or 2-halo; R₂ and R₃are, independently, H, halo, C₁-C₆ alkyl, or C₁-C₆ alkenyl, said alkyland alkenyl groups optionally substituted as described above; R₄ is H,vinyl, cyano, halo, hydroxy, or C₁-C₆ alkyl; and R′ is —(CH₂)_(n)-G,where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethylmorpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 4-methyl or 4-halo; R₂ and R₃are H; R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups or R′ is —(CH₂)_(n)-G,where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethylmorpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 2-methyl; R₂ is 4-halo; R₃ is H;R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 2-halo; R₂ is 4-methyl; R₃ is H;R₄ is H, OH, halo, or methyl; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 2-methyl; R₂ is 4-chloro; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-2, where R₁ is 2-chloro; R₂ is 4-methyl; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl,(2-tetrahydrofuryl)methyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ and R₃are H; R₄ is H, vinyl, cyano, halo, hydroxy, or methyl; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is6-methyl or 6-halo; R₃ is H; R₄ is H, hydroxy, or methyl; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is6-methyl or 6-halo; R₃ is H; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G,where n is 1 or 2, and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is6-methyl or 6-halo; R₃ is H; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G,where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl or 4-halo; R₂ is H,6-methyl, or 6-halo; R₃ is H, C₁-C₃ alkyl, dimethylamino methyl;chloromethyl, or bromomethyl; R₄ is H or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups or R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-methyl; R₂ is 6-chloro; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl, or R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-3, where R₁ is 4-chloro; R₂ is 6-methyl; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl, or R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-4, where R₁ is 5-methyl or 4-halo; R₂ is6-methyl or 6-halo; R₃ is H; 4 is H, hydroxy, halo, C₁-C₆ alkyl, orC₁-C₆ alkenyl; and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and Gis N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl,2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-4, where R₁ is 5-methyl; R₂ is H, 6-methyl, or6-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups, or R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-4, where R₁ and R₂, at positions 5 and 6, arefused benzo or pyrido; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups, or R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-4, where R₁ is 5-chloro; R₂ is H, 6-methyl, or6-chloro; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups, or R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl.

In a more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is 3-(C₁-C₄ alkyl), 3-(C₁-C₄alkenyl), or 3-halo; R₂ and R₃ are H; R₄ is H, vinyl, cyano, halo,hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted withone or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl,2-tetrahydrofuryl, or 4-imidazolyl.

In a more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is 3-methyl or 3-halo; R₂ is5-methyl or 5-halo; R₃ is H; R₄ is H, OH, or methyl; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups, or R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or4-imidazolyl or R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is 3-methyl; R₂ is 5-chloro; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ and R₂, at positions 2 and 3, arefused benzo, pyrido, pyrrolo, or imidazolo, optionally substituted withhalogen, methyl, halomethyl, or hydroxy; R₃ is H; R₄ is H, OH, ormethyl; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a still more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is 3-methyl; R₂ is 5-chloro; R₃ isH; R₄ is H, OH, or methyl; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is H, 2-methyl, 2-nitro,2-methylcarbamoyl, or 2-halo; R₂ is 3-methyl or 3-chloro, and R₃ is H,5-methyl, or 5-chloro; R₄ is H, OH, or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups or R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, 2-tetrahydrofuryl, or 4-imidazolyl or R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is H, 2-acetyl, 2-acetamido,2-dimethylamino, or 2-halomethyl; R₂ is 3-methyl or 3-chloro, and R₃ isH, 5-methyl, or 5-chloro; R₄ is H or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another still more specific embodiment, this invention provides acompound according to formula IXB-5, where R₁ is 3-methyl; R₂ is H or5-chloro; R₃ is H; R₄ is H; and R′ is isopropyl, 1-hydroxy-2-propyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is H, 2-bromomethyl, 2-ethynyl,2-cyano; R₂ is 3-chloro; R₃ is H or 5-methyl; R₄ is H or methyl; and R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is H or 2-chloro; R₂ is 3-chloro;R₃ is H or 5-chloro; R₄ is H or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-5, where R₁ is H or 2-chloro; R₂ is 3-chloro;R₃ is H or 5-chloro; R₄ is H or methyl; and R′ is —(CH₂)_(n)-G, where nis 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-6, where R₁ is H, 4-acetyl, 4-acetamido,4-dimethylamino, 4-C₁-C₄ alkyl, alkenyl, alkynyl, or cycloalkyl, or4-halomethyl; R₂ is H, 5-methyl or 5-halo, and R₃ is H, 6-methyl, or6-chloro; R₄ is H, hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-6, where R₁ is 4-methyl; R₂ is H or 5-chloro;R₃ is H or 6-chloro; R₄ is H or methyl; and R′ is isopropyl,1-hydroxy-2-propyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-6, where R₁ is H, 4-bromomethyl, 4-ethynyl,4-cyano; R₂ is H, 5-methyl, or 5-chloro; R₃ is H, 6-acetyl, 6-acetoxy,6-acetamido, or 6-methylcarbamoyl; R₄ is H, vinyl, chloromethyl,hydroxy, or methyl; and R′ is C₁-C₆ alkyl, optionally substituted withone or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-6, where R₁ and R₂, at positions 4 and 5, arefused benzo; R₃ is H or 6-methyl; R₄ is H, halo, halomethyl, hydroxy, ormethyl; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups or R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl, or R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundaccording to formula IXB-6, where R₁ and R₂, at positions 4 and 5, are(2,3) fused imidazolo, pyrido, or pyrrolo; R₃ is H or 6-methyl; R₄ is H,halo, halomethyl, or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

Prophetic examples of additional compounds of formula IXB are shownbelow

In another generic embodiment, this invention provides a compound offormula X

where M, Q, T, U, V, W, X, Y, and Z represent N, CH, orCR_(1, 2, 3, or 4), where R₁-R₄ are defined as for formula I.

In a subgeneric embodiment, this invention provides a compound offormula XA where M, Q, T, U, V, W, X, Y, and Z are all CH orCR_(1, 2, 3, or 4).

In another subgeneric embodiment, this invention provides a compound offormula XB,

where all substituents are as defined for formula I, and where at leastone of M, Q, T, U, V, W, X, Y, and Z is N, provided that no ringcontains 2 adjacent nitrogen atoms.

In one subgeneric embodiment, this invention provides a compound offormula XA, where R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,oxazolidinonyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, pyrrolidinonyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolinyl, isothiazolidinyl, isothiazolidinonyl,imidazolinyl, imidazolyl, imidazolinonyl, pyridyl, pyrazyl, pyranyl,pyridazolyl, piperidinonyl, morpholyl, 2,6-dimethyl morpholyl,tetrahydrofuryl, piperazinyl, 1-methyl-piperazin-4-yl, piperazinonyl,2-pyrrolidonyl, tolyl, phenyl, piperidinyl, pyrimidinyl, pyrazolyl,isoxazolyl, isoxazolinyl, isoxazolidinyl, isoxazolidinonyl,isothiazolinyl, isothiazolidinyl, indolyl, oxindolyl, isoindolyl,quinolyl, isoquinolyl, or naphthyl.

In another preferred embodiment, this invention provides a compound offormula XA, where R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl.

In another preferred embodiment, this invention provides a compound offormula XA, where R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another preferred embodiment, this invention provides a compound offormula XA, where R₁ and R₂ are both ortho substituents.

In another preferred embodiment, this invention provides a compound offormula XA, where R₄ and R₅ occupy the 3- and 5-positions.

In a more specific embodiment, this invention provides a compound offormula XA, where R₁ and R₂ are as defined for formula I; R₄ and R₅ areboth H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ and R₂ are defined as in formula XA; R₄ and R₅are both H; and R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, both optionallysubstituted as described above.

In a still more specific embodiment, this invention provides a compoundof formula XA, where R₁ and R₂ are H, halo, or C₁-C₃ alkyl; R₄ and R₅are both H; and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a preferred and more specific embodiment, this invention provides acompound of formula XA, in which R₁ is 2-halo; R₂ is 6-methyl; R₄ and R₅are, independently, H, C₁-C₃ alkyl, or halo; and R′ is isopropyl ormono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄ andR₅ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is isopropyl ormono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are,independently, methyl or halo; and R′ is isopropyl or mono- ordi-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are,independently, methyl or chloro; and R′ is isopropyl or mono- ordi-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ and R₂ are H; R₄ and R₅ are 3-chloroand 5-methyl; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ and R₂ are H; R₅ is 2-chloro or3-chloro; R₄ is H; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄alkyl.

In another more preferred specific embodiment, this invention provides acompound of formula XA, in which R₁ and R₂ are H; R₅ is 2-methyl or3-methyl; R₄ is H; and R′ is isopropyl or mono- or di-hydroxy C₁-C₄alkyl.

In another more preferred subgeneric embodiment, this invention providesa compound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄and R₅ are, independently, H, C₁-C₃ alkyl, or halo; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ is C₂-C₆ alkenyl, C₂-C₆ alkynyl, or C₁-C₆cycloalkyl; R₂-R₅ are H; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino; R₂-R₅ are H and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl; R₂-R₅ are H and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂-R₅are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both halogen; R₅ is 2-methyl; andR₄ is H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 2-chloro; R₄ is3-methyl; R′ is —(CH₂)_(n)-G, where n is 1, and G is piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl, ortetrahydrofuryl, or R′ is C₁-C₆ alkyl, optionally substituted with oneor two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 3-methyl; R₄ is6-(2-chloroethyl); R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-hydroxymethyl; R₅ is 4-CF₃; R₂ and R₄are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 3-methyl; R₄ is5-chloro; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another specific embodiment, this invention provides a compound offormula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ are H;and R′ is —(CH₂)_(n)-G, where n is 1, and G is 3-methyl-2-isothiazolyl,3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl,3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound offormula XA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl; R₂; R₄;and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl;oxazolyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl,thiazolidinyl, thiazolidinonyl, isothiazolyl, isothiazolinyl,isothiazolidinyl, isothiazolidinonyl, indolyl, indolyl, oxindolyl,isoindolyl, quinolyl, isoquinolyl, or naphthyl, or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 3-chloro; R₂; R₄ and R₅ are H; R′is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-chloro; R₂ is 6-methyl; R₄ andR₅ are H; R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 4-chloro; R₂; R₄ and R₅ are H; R′is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ and R₂ are 2,6-di-chloro; R₂; R₄ andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl;piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-bromo; R₂; R₄ and R₅ are H; andR′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 3-bromo; R₂; R₄ and R₅ are H; andR′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 4-bromo; R₂; R₄ and R₅ are H; andR′ is —(CH₂)_(n)-G, where n is 1, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-, 3-, or 4-bromo; R₂; R₄ and R₅are H; and R′ is —(CH₂)_(n)-G, where n is 1, and G is R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula XA, in which R₁ is 4-bromo; R₂ is 2-methyl; R₅ is 3-methyl;R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula XA, in which R₁ is 2-bromo; R₂ is 6-methyl; R₅ is 3-methyl;R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another specific embodiment, this invention contemplates the compoundof formula XA, in which R₁ is 3-bromo; R₂ is 6-methyl; R₅ is 3-methyl;R₄ is H, 5-methyl, or 5-halo; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-chloro; R₂ is 4-chloro; R₄ andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-methyl; R₂ is 6-methyl; R₄ andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is4-imidazolyl, 4-morpholyl, 4-(2,6-dimethyl morpholyl),2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ areH; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-CF₃; R₂; R₄ and R₅ are H; andR′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl,4-morpholyl, 4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl,piperazin-1-yl, 1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl orhalogen; R₅ is 2-chloromethyl, 4 is H; and R′ is —(CH₂)_(n)-G, where nis 1 or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl,3-piperidyl, or 4-piperidyl or R′ is isopropyl or mono- or di-hydroxyC₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl orhalogen; R₅ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where nis 1 or 2; and G is 2-pyrimidyl, 4-pyrimidyl, 2-morpholyl, or3-morpholyl or R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl orhalogen; R₅ is 3-methyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where n is 1or 2; and G is 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-piperidyl,3-piperidyl, or 4-piperidyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂, in positions 2 and 6, are methyl orhalogen; R₅ is 3-fluoromethyl; and R₄ is H; R′ is —(CH₂)_(n)-G, where nis 1 or 2; and G is 4-bromo-2-pyrimidyl, 2-chloro-4-pyrimidyl,2-morpholyl, or 3-morpholyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3-cyano; R₂ is H or 6-methyl; R₄ and R₅are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3-hydroxy; R₂ is H or 6-methyl; R₄ and R₅are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-hydroxy; R₂ is H or 2-methyl; R₄ and R₅are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinylor R′ is isopropyl or mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 2-methyl;R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2;and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropylor mono- or di-hydroxy C₁-C₄ alkyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 2-methyl;R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2;and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is isopropylor mono- or di-hydroxy C₁-C₄ alkyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-ethoxymethyl; R₂ is H or2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R is 2-, 3-, or 4-methoxymethyl; R₂ is H or2-methyl; R₄ and R₅ are H, halo, or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3-(2-methoxyethyl); R₂ is H, 2-methyl, or6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-(2-methoxyethyl); R₂ is H, 2-methyl, or6-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is1 or 2; and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ isH or 6-methyl; R₄ and R₅ are H; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ isH or 6-methyl; R₅ is 3-methyl; R₄ are 5-methyl, 5-halo, or H; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ isH; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl;R₂ is H or 6-methyl; R₅ is H or 3-methyl, R₄ is H; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂ is H or6-methyl, R₅ is H, 3-chloro, or 3-methyl; R₄ is H or 5-methyl; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂ is H or6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂ isH or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is 4-imidazolyl, 4-morpholyl,4-(2,6-dimethyl morpholyl), 2-tetrahydrofuryl, piperazin-1-yl,1-methyl-piperazin-4-yl, piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3- or4-dimethylaminocarbonyl; R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ isH or 5-chloro; and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl;R₂ is H or 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3- or 4-chloroacetyl; R₂ is Hor 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3- or 4-acetoxy; R₂ is H or6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3- or 4-fluoromethyl; R₂ is Hor 6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-cyano; R₂ is H or 6-methyl; R₅ is H or3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups, or R′ is —(CH₂)_(n)-G,where n is 1 or 2; and G is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3- or 4-ethoxy; R₂ is H or 6-methyl;R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, wheren is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethylmorpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-vinyl; R₂ is H or 6-methyl;R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, wheren is 1 or 2; and G is 4-imidazolyl, 4-morpholyl, 4-(2,6-dimethylmorpholyl), 2-tetrahydrofuryl, piperazin-1-yl, 1-methyl-piperazin-4-yl,piperazin-2-on-4-yl, or 2-pyrrolidonyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂ is H or6-methyl; R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-methoxy; R₂-R₅ are H; R′ is—(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-methyl; R₂ is 4-methylsulfonyl; R₄ andR₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1, and G is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂ is H or 6-methyl;R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, wheren is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl;cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-bromo; R₂ is H or 6-methyl;R₅ is H or 3-methyl; R₄ is H or 5-chloro; and R′ is —(CH₂)_(n)-G, wheren is 1, and G is cyclopentyl, cyclopenten-3-yl, cyclopentadien-4-yl;cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-chloro; R₂ is 3-, 4-, 5-, or6-cyclopropyl, R and R₅ are H, halo, or methyl; and R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3-cyclopropyl; R₂-R₅ are H; and R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3-cyclopropyl; R₂ is 2-, 4-, 5-, or6-chloro; R₄ and R₅ are H; and R′ is C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-chloro; R₂ istrans-4-(2-methylcyclopropyl); R4 and R5 are H; R′ is —(CH₂)_(n)-G,where n is 1, and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl,oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-cyclopropyl; R₂ is 2- or 3-chloro; R₄and R₅ are H, halo, or C₁-C₃ alkyl; and R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-isopropyl; R₂ is 2-chloro; R₅ is 2- or3-chloro; R₄ is 5- or 6-methyl; and R′ is —(CH₂)_(n)-G, where n is 1,and G is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl or R′ is C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both halogen; R₅ is 3-methyl; R₄is H; and R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 3-chloro; R₄ is5-methyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 2-(2-chloroethyl); 4is 3-methyl; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-hydroxymethyl; R₂ is 4-CF₃; R₄ and R₅are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are both H; R₅ is 3-chloro; R₄ is5-methyl; and R′ is —(CH₂)_(n)-G, where n is 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another more specific embodiment, this invention provides a compoundof formula XA, in which one or both of R₁ and R₂ are CF₃; R₄ and R₅ areH; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another subgeneric embodiment, this invention provides a compound offormula XA, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂; R₅; andR₄ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a more specific embodiment, this invention contemplates the compoundof formula XA, in which R₁ is 4-chloro; R₅ is 3-chloro; R₂ and R₄ are H;R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-, 3-, or 4-fluoro; R₂, R₄ andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is fluoro; R₂ is methyl; R₄ and R₅are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 6-chloro; R₂, R₄ and R₅ are H; R′is —(CH₂)_(n)-G, where n is 1 or 2; and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-bromo; R₂ is methyl; R5; and R₄are H; R′ is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 3-bromo; R₂; R₄ and R₅ are H; R′is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 4-bromo; R₂, R₄ and R₅ are H; R′is —(CH₂)_(n)-G, where n is 2, and G is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 2-(2-chloroethyl); R₂ is6-chloro; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and G ispyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl or R′ is C₁-C₆ alkyl,optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates thecompound of formula XA, in which R₁ is 4-(3-chloropropyl); R₂ is2-bromomethyl; R₄ and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 2, and Gis pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-CF₃; R₂, R₄ and R₅ are H; R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is isothiazol-4-yl,isoxazol-4-yl, oxazol-2-yl, 2-oxazolin-4-yl, oxazolidin-5-yl, orthiazol-2-yl, or R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-cyano; R₂ is 2-methyl; R₄ and R₅ are Hor methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-methyl; R₂ is 4- or 5-hydroxy; R₄ and R₅are H or methyl; R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-hydroxymethyl; R₂-R₅ are H; R′ is—(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In another specific embodiment, this invention provides a compound offormula XA, in which R₁ is 2-methoxy; R₂ is H, halo, or methyl; R₄ andR₅ are H or methyl; R′ is —(CH₂)_(n)-G, where n is 2, and G is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl,or R′ is C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In a still more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-methoxy; R₂-R₅ are H; R′ is—(CH₂)_(n)-G, where n is 2, and G is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-dimethylamino; R₂,R₄, and R₅ are H; R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or4-dimethylaminocarbonyl; R₂ is H or 6-methyl, R₄ and R₅ are H, halo, ormethyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl, or R′ is C₁-C₆ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-methyloxycarbonyl;R₂ is H, 6-methyl, or 6-halo; R₄ and R₅ are H, halo, or methyl; and R′is —(CH₂)_(n)-G, where n is 1 or 2; and G is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl, or R′ isC₁-C₆ alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₄, andR₅ are H; and R′ is C₁-C₆ alkyl, optionally substituted with one or twoor hydroxyl groups.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂, R₄, andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 2, and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 4-dimethylamino; R₂ is 2-methyl;R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 4-dimethylaminocarbonyl; R₂ is2-methyl; R₄ and R₅ are H or methyl; and R′ is —(CH₂)_(n)-G, where n is1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 4-methyloxycarbonyl; R₂ is H ormethyl; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, andG is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetyl; R₂, R₄, andR₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-acetoxy; R₂; R₅; andR₄ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, in which R₁ is 2-, 3-, or 4-CH₂F; R₂; R₄; and R₅are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G isN-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-cyano; R₂-R₅ are H; and R′ is—(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-ethoxy; R₂-R₄ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-trifluoromethoxy; R₂-R₅ areH; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is N-pyrrolidinonyl,4-morpholyl, 2,6-dimethyl-4-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-chloromethoxy; R₂-R₅ are H;and R′ is —(CH₂)_(n)-(G, where n is 1 or 2, and G is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, morpholyl, orimidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₅ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is 5-oxazolidinyl,4-thiazolyl, 3-thienyl, 2-furyl, 3-pyrrolyl, 2-pyrrolidinyl,N-pyrrolidinonyl, N-morpholyl, or 4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3- or 4-methylsulfonyl R₂ is 2-(2-methylcyclopropyl); R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or2, and G is 3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl,3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl,N-pyrrolidonyl, or m-tolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2-, 3-, or 4-methoxy; R₂-R₅ are H; and R′is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 4-bromo or 4-bromomethyl; R₂-R₅ are H; andR′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is cyclopentyl,cyclopenten-3-yl, cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2- or 3-chloro; R₂ is4-(2-cyclopropylethyl); R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where nis 1 or 2, and G is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is cyclopropyl or cyclopropylmethyl; R₂-R₅are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, and G is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is trans-3-(2-methylcyclopropyl); R₂ is6-chloro; R₄ and R₅ are H; and R′ is —(CH₂)_(n)-G, where n is 1 or 2,and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 3- or 4-cyclopropyl; R₂ is 5-chloro; R₅ is2-(2-fluoroethyl); and R₄ is H; and R′ is —(CH₂)_(n)-G, where n is 1 or2, and G is N-pyrrolidinonyl, 4-morpholyl, 2,6-dimethyl-4-morpholyl, or4-imidazolyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is 2- or 3-cyclopropyl; R₂ is 6-chloro; R₅ is3-chloro; R₄ is 5-methyl; and R′ is —(CH₂)_(n)-G, where n is 1 or 2, andG is 3-methyl-2-pyridyl, 3-methyl-2-piperazinyl,3-methylpiperazin-2-on-1-yl, 3-methyl-1-piperidinyl,3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl, 3-methyl-2-furyl,3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another embodiment, this invention provides a compound of formula XA,in which R₁ and R₂ are halogen or methyl; R₄ and R₅ are H; and R′ ismethyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is halogen or methyl; R₂-R₅ are H; and R′ ismethyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ is bromo; R₂-R₅ are H; and R′ is isopropyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areC₁-C₆ alkyl; and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 4-methoxybutyl.

In another more specific embodiment, this invention provides a compoundof formula XA, in which R₁ and R₂ are halogen or methyl; R₄ and R₅ areH; and R′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula XA, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused(4,5)-imidazolo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-Butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused(2,3)-furyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused(2,3)-pyrido; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, are fused(3,4)pyrrolyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 2 and 3, are fusedcyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, are fusedcyclopentyl; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 2 and 3, arebenzo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 2 and 3, arebenzo, substituted at one or both ortho positions; R₄ and R₅ are H; andR′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XA, where R₁ and R₂, at positions 3 and 4, arebenzo; R₄ and R₅ are H; and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

The prophetic examples below show specific embodiments of thisinvention.

In additional subgeneric embodiments, this invention providesaza-substituted compounds of the types shown below, where substituentsR₁-R′ are as defined above.

In one more specific embodiment, this invention provides a compound offormula XB1, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB2, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB3, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB4, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB5, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB6, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB7, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB8, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB9, where R₁-R₄ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB10, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound offormula XB11, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound offormula XB12, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB1, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB2, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB3, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB4, where R₁-R₄ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB5, where R₁-R₅ are, independently, H, methyl, halo, nitro,cyano, 1-propynyl, amino, dimethylamino, or acetamido, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB6, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB7, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB8, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB9, where R₁-R₅ are, independently, H, methyl, halo, acetyl,acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is —(CH₂)_(n)-G,as described above, or C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB10, where R₁-R₅ are, independently, H, methyl, halo,acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB11, where R₁-R₅ are, independently, H, methyl, halo,acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB12, where R₁-R₅ are, independently, H, methyl, halo,acetyl, acetoxy, methyloxycarbonyl, or methylsulfonyl, and R′ is—(CH₂)_(n)-G, as described above, or C₁-C₆ alkyl, optionally substitutedwith one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound offormula XB1, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB2, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB3, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB4, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB5, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB6, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB7, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB8, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB9, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB10, where R₁-R₅ are, independently, H, halo, or C₁-C₅alkyl, cycloalkyl, or alkenyl, optionally substituted with halogen,alkoxy, hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above,or C₁-C₆ alkyl, optionally substituted with one or two or hydroxylgroups.

In one more specific embodiment, this invention provides a compound offormula XB11, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In one more specific embodiment, this invention provides a compound offormula XB12, where R₁-R₅ are, independently, H, halo, or C₁-C₅ alkyl,cycloalkyl, or alkenyl, optionally substituted with halogen, alkoxy,hydroxy, or phenyl, and R′ is —(CH₂)_(n)-G, as described above, or C₁-C₆alkyl, optionally substituted with one or two or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XB1, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB2, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB3, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB4, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB5, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB6, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB7, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB8, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB9, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In another more specific embodiment, this invention provides a compoundof formula XB10, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XB111, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

In a still more specific embodiment, this invention provides a compoundof formula XB12, where R₁-R₅ are, independently, H, halo, methyl, orhalomethyl, and R′ is C₁-C₆ alkyl, optionally substituted with one ortwo or hydroxyl groups.

Additional subgeneric embodiments are shown below.

In an even more specific and preferred embodiment, this inventionprovides a compound of formula XB1, where R₁-R₄ are, independently, H,chloro, or methyl, R₅ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB2, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB3, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB4, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB5, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB6, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB7, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB8, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB9, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB10, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB11, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

In an additional more specific and preferred embodiment, this inventionprovides a compound of formula XB12, where R₁-R₅ are, independently, H,chloro, or methyl, R₄ is H, and R′ is C₁-C₄ alkyl, optionallysubstituted with one or two or hydroxyl groups.

The prophetic examples below provide specific examples of subgenericstructures XB-1-XB-12.

In another generic embodiment, this invention provides a compound offormula XI below,

where the dashed bond represents an optional double bond, where symbolsL, T, U, V, and W-Z represent N, CH, or CR_(1, 2, or 4), provided thatno two nitrogen atoms are adjacent, where R₁-R₄ are, independently,hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl;C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl;CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₆R₇,—CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, whereR₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ andR₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which theyare attached, form an additional, five- or six-membered ring, optionallycontaining one or two heteroatoms selected from O, N, and S, which ringmay be aromatic or aliphatic, and which ring is fused in the case of R₁and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl,wherein all alkyl, alkenyl, and cycloalkyl groups and all rings areoptionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, ortrifluoromethyl groups; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R′ is—(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring ora 9- to 14-member fused ring system, wherein each ring optionallycontains 1-3 heteroatoms selected independently from O, N, and S;wherein each ring is optionally substituted with 1-3 groups selectedindependently from the following: halogen, hydroxy, cyano, oxo, andC₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substitutedwith one to three halogen atoms; and wherein each ring optionallycontains one or more double bonds.

In one subgeneric embodiment, this invention provides a compound offormula XIA-1,

where R₁-R′ are as defined above for formula I.

In a more specific embodiment, this invention provides a compound offormula XIA-1, where R₁-R₄ are as described above for formula I, andwhere R′ is C₁-C₆ alkyl, optionally substituted with one or two orhydroxyl groups, or R′ is —(CH₂)_(n)-G, where n is 1 or 2; and G isisothiazolyl, isoxazolyl, isoxazolidinyl, isoxazolidinonyl, oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolyl, thienyl, furyl,pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, thiazolinyl,thiazolidinyl, thiazolidinonyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl orO—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, where R₂-R₅ are H and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a more specific embodiment, this invention contemplates a compound offormula XIA-1, where R₁-R₄ are H and R′ is 2-(2-furyl)ethyl,2-hydroxyethyl, or 2,3-dihydroxy-1-propyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 3and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 3and 4, are benzo, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 3and 4, are 2,3-pyrido, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 3and 4, are 2,3-pyrrolo, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 4and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ together, at positions 3and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is2-hydroxyethyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 2-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 2-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl,phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-acetyl, R₂, R₃, and R are H.R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-bromo, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)and B is pyridyl, piperazinyl, piperazinonyl,piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, orpyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and Bis isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are both H. R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, or naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 2-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 4-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 5-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 4-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 5-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 2-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIA-1, in which R₁ is 3-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl,phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 4-bromo, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)and B is pyridyl, piperazinyl, piperazinonyl,piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, orpyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and Bis isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is methyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is ethyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XIA-1, in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-(methylcarbamoyl), R₂ is5-fluoro, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-acetamido, R₂ is 5-fluoro,R₃ and R₄ are H, and R′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ are 4-fluoro and 5-fluoro,R₃ and R₄ are H, and R′ is 2-hydroxyethyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ are 4-chloro and 5-chloro,R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ are 4-fluoro and 5-fluoro,R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 2-methoxymethyl, and R₂ is3-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 2-ethoxymethyl, and R₂ is3-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-methoxymethyl, R₂ is4-chloro, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-nitro, R₂ is 4-methoxy, R₃and R₄ are H, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 5-nitro, R₂-R₄ are H, and R′is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-cyano, R₂-R₄ are H, and R′is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 3-(2-methoxyethenyl), R₂-R₄are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ is 4-cyano, R₂-R₄ are H, and R′is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-1, in which R₁ and R₂ are 3-chloromethyl and4-chloromethyl, R₃ and R₄ are H, and R′ is 3-hydroxypropyl.

In another subgeneric embodiment, this invention provides a compound offormula XIA-2, where R₁-R′ are defined as for formula I.

In a more specific embodiment, this invention provides a compound offormula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 1,and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 2,and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-2 where R₁-R₄ are H and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound offormula XIA-2 where R₁-R₄ are H and R′ is isopropyl, 2-butyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-duhydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-2, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIA-2, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a more specific embodiment, this invention provides a compound offormula XIA-2, where R is 4-acetyl, R₂, R₃, and R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-2, where R₁ is 4-bromo, R₂, R₃, and R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-isothiazolyl,3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl, 3-methyl-2-pyrrolyl,3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2, where R₁ is 5-bromo, R₂ and R₃ are H, R₄ is2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2, where R₁ is 5-cyano, R₂ is H, R₃ is2-trifluoromethyl, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, andB is 5-methyl-2-furyl, 5-methyl-2-pyrrolyl, or 3-pyrrolyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2, where R₁ is 4-fluoro, R₂ is 5-fluoro, R₃ is3-acetamido, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is5-methyl-2-furyl, 5-methyl-2-pyrrolyl, or 3-pyrrolyl.

In a more specific embodiment, this invention contemplates a compound offormula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B, where n is 1,and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 where R₁-R₄ are H and R′ is —(CH₂)_(n)—B,where n is 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidinyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 where R₁-R₄ are H and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-duhydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2, where R₁ and R₂ together, at positions 3 and4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 4and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is2-hydroxyethyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula XIA-2, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIA-2, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2, where R₁ and R₂ together, at positions 3 and4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is1-hydroxy-butan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 4and 5, are fused (2,3)-furyl, R₃ and R₄ are H, and R′ is1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused (2,3)thienyl, R₃ and R₄ are H, and R′ is2-hydroxyethyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together, at positions 3and 4, are fused cyclopentyl, R₃ and R₄ are H, and R′ is 4-hydroxybutyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together are fused furyl,R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ and R₂ together are fusedcyclopentyl, R₃ and R₄ are H, and R′ is 1,2-dihydroxybutan-4-yl.

In another specific embodiment, this invention contemplates a compoundof formula XIA-2 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidinyl.

In a more specific embodiment, this invention provides a compound offormula XIA-2 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In another more specific embodiment, this invention contemplates acompound of formula XIA-2 in which R₁ is 3-CH₂F, R₂ is 5-cyano, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In another generic embodiment, this invention provides a compound offormula B, where R₁-R′ are defined as for formula A, where the dashedline represents an optional double bond, and where symbols L, T, U, V,and W-Z represent N, CH, or CR_(1, 2, or 4), provided that at least oneof L, T, U, V, and W-Z is N, and further provided that no two nitrogenatoms are adjacent.

In one subgeneric embodiment, this invention provides a compound offormula XIB-1,

where all substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound offormula XIB-1, where R₁-R₄ are, independently, H, C₁-C₆ alkyl, hydroxy,or halogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, 1-pyrrolidonyl,2,6-dimethyl-4-morpholyl, 4-morpholyl, furyl, tetrahydrofuryl, orpyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, where R₁-R₄ are, independently, H, C₁-C₆ alkyl,hydroxy, or halogen, and R′ is C₁-C₄ alkyl, optionally substituted withone or two halogen atoms, hydroxy groups, or C₁-C₃ alkoxy groups.

In a still more specific embodiment, this invention provides a compoundof formula XIB-1, where R₁-R₄ are, independently, H. C₁-C₄ alkyl,hydroxy, or halogen, and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-1 where one of R₁ and R₂ is H and the other is amino,methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino; R₃-R₄are, independently, H, chloro, methyl, or hydroxy; and R′ is C₁-C₆alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, where one of R₁ and R₂ is H and the other is nitro,cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl; R₃-R₄ are,independently, H, chloro, methyl, or hydroxy; and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl, R₃ and R₄ are, independently, H, chloro, methyl, orhydroxy; and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, where R₁ and R₂ are fused benzo; R₃ and R₄ are,independently, H, chloro, methyl, or hydroxy; and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, wherein R₁ and R₂ are, independently, H or halogen, R₃and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In a more specific embodiment, this invention provides a compound offormula XIB-1, where R₁-R₃ are H, R₄ is 2-halo, 2-cyano, 2-hydroxy, or2-methoxy, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is4-methyl-1-piperazinyl, 1-piperidinyl, piperidinonyl, 4-morpholyl,2,6-dimethyl-4-morpholyl, 2-furyl, 2-tetrahydrofuryl, 1-pyrrolidonyl, orpyrimidinyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-1, where R₁ is halo, R₂-R₄ are H and R′ is —(CH₂)_(n)—B,where n is 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl,piperidinyl, piperidinonyl, morpholyl, furyl, tetrahydrofuryl, orpyrimidinyl.

In a still more specific embodiment, the invention contemplates acompound of formula XIB-1, where R₁ is chloro or bromo; R₂-R₄ are H; andR′ is isopropyl, 2-hydroxyethyl, 1-hydroxy-2-propyl, or2,3-dihydroxy-1-propyl.

In another embodiment, this invention provides a compound of formulaXIB-2,

where substituents are defined as for formula I.

In a more specific embodiment, this invention provides a compound offormula XIB-2, where R₁-R₄ are, independently, H or halogen, and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2-methoxyethyl,1-hydroxy-2-propyl,1,2-dihydroxy-3-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIB-2, where one of R₁ and R₂ is H and the other is amino,methyl amino, dimethylamino, dimethylaminomethyl, or acetylamino, R₃-R₄are H, and R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIB-2, where one of R₁ and R₂ is H and the other is nitro,cyano, methylcarbamoyl, dimethylcarbamoyl, or aminosulfonyl, R₃-R₄ are Hand R′ is C₁-C₆ alkyl, optionally substituted with halogen, C₁-C₃alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIB-2, where R₁ and R₂ are H, R₃ is methyl, methoxy,acetamido, or acetyl, R₄ is nitro, cyano, halo, halomethyl,dimethylamino, or methylaminocarbonyl, and R′ is —(CH₂)_(n)—B, where nis 1 or 2, and B is pyridyl, piperazinyl, piperazinonyl, piperidinyl,piperidinonyl, morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIB-2, where R₁ and R₂ are fused cyclohexyl or areboth H, R₃ and R₄ are H, and R′ is isopropyl or 1-hydroxy-2-propyl.

Additional embodiments of generic structure B are shown below.

In more specific embodiments, the invention provides compounds accordingto any of formulas XIB-1 to XIB-43, wherein R₁-R₄ are all independentlymethyl, methoxy, ethyl, vinyl, ethynyl, halo, or H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, cyclopentyl, cyclopentenyl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In additional more specific embodiments, the invention providescompounds according to any of formulas XIB-1 to XIB-43, wherein R₁-R₄are all independently halo, halomethyl, dihalomethyl, or H, and R′ is—(CH₂)_(n)—B, where n is 1 or 2, and B is phenyl, pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidinyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas XIB-1 to XIB-43, where R₁ isbromo; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas XIB-1 to XIB-43, where R₁ ischloro; R₂-R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas XIB-1 to XIB-43, where R₃ ischloro; R₁, R₂, and R₄ are all H; and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas XIB-1 to XIB-43, where R₄ ischloro or hydroxy; R₁-R₃ are all H; and R′ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas XIB-1 to XIB-43, where R₁-R₄ are all H andR′ is isopropyl, 1-hydroxy-2-propyl, or 2,3-dihydroxy-1-propyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas XIB-1 to XIB-28 and XIB-30 to XIB-42, whereR₁-R₃ are all H; R₄ is ortho to the amide group and is chloro orhydroxy; and R′ is isopropyl, 1-hydroxy-2-propyl,2,3-dihydroxy-1-propyl, or (2-tetrahydrofuryl)methyl.

Additional contemplated examples of compounds according to formulasXIB-1 to XIB-43 are shown below.

Additional contemplated compounds for subgeneric embodiments XIA-1 andXIA-2 are shown in the tables below

Cpd # Structure 1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

In another generic embodiment, this invention provides a compound offormula XII below, where the dashed bond represents an optional doublebond, and where symbols T-Z represent N, CH, or CR_(1, 2, or 4), that atmost two of W, X, Y, and Z and at most 2 of T, U, and V are N;

where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro;cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—;C₁-C₅ alkyl-C(O)O—; —NR₆R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉;CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄alkyl; or any of the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ areattached to adjacent carbons and, together with the ring atoms to whichthey are attached, form an additional, fused, five- or six-memberedring, optionally containing one or two heteroatoms selected from O, N,and S, which ring may be aromatic or aliphatic; wherein all alkyl,alkenyl, and cycloalkyl groups and all rings are optionally substitutedwith 1-3 halogen atoms; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R′ is—(CH₂)_(n)—B where n is 1 or 2 and B is a five- or six-membered ring ora 9- to 14-member fused ring system, wherein each ring optionallycontains 1-3 heteroatoms selected independently from O, N, and S;wherein each ring is optionally substituted with 1-3 groups selectedindependently from the following: halogen, hydroxy, cyano, oxo, andC₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substitutedwith one to three halogen atoms; and wherein each ring optionallycontains one or more double bonds.

In one subgeneric embodiment, this invention provides a compound offormula XIIA-1,

where all substituents are defined as for formula XII.

In a more specific embodiment, this invention provides a compound offormula XIIA-1 where R₃ and R₄ are both H and R′ is —(CH₂)_(n)—B, wheren is 1 or 2 and B is defined as above.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 where R′ is C₁-C₆ alkyl or O—C₁-C₆ alkyl, bothoptionally substituted as described above.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 where R₃ and R₄ are both H and R′ is C₁-C₆ alkyl orO—C₁-C₆ alkyl, both optionally substituted as described above.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1, where R₂-R₄ are H and R′ is C₁-C₆ alkyl, optionallysubstituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 2-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 4-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 5-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 4-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 5-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 2-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl,phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-bromo, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 1, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 1, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 1, and Bis isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 1, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both halogen, R₃ is 2-methyl,and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-(2-chloroethyl), R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-CF₃, R₃ is 2-hydroxymethyl, R₂ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are both H, R₃ is 3-methyl, R₄ is2-chloro, R′ is —(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is isothiazolyl, isoxazolyl, oxazolyl,oxazolidyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl; R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, pyrimidyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,pyrrolidinonyl, pyrazolyl, imidazolyl, imidazolinonyl; oxazolyl,oxazolinyl, oxazolidinyl, oxazolidinonyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, isoxazolidinonyl, thiazolyl, thiazolinyl, thiazolidinyl,thiazolidinonyl, isothiazolyl, isothiazolinyl, isothiazolidinyl,isothiazolidinonyl, indolyl, indolyl, oxindolyl, isoindolyl, quinolyl,isoquinolyl, and naphthyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 2-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 4-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 5-chloro, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 4-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 5-bromo, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 2-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention contemplates thecompound of formula XIIA-1 in which R₁ is 3-chloro, R₂ is 4-chloro, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which one or both of R₁ and R₂ are CF₃, R₃ and R₄are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl,phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-CF₃, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-hydroxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is 3-methyl-2-pyridyl,3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-dimethylamino, R₂, R₃, andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-dimethylaminocarbonyl, R₂,R₃, and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-methyloxycarbonyl, R₂, R₃,and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-acetyl, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 4-acetoxy, R₂, R₃, and R₄ areH, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention contemplates acompound of formula XIIA-1 in which R₁ is 3-CH₂F, R₂, R₃, and R₄ are H,R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl,oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyano, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-ethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-chloromethoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 2-methyl, R₂ is 4-methylsulfonyl, R₃and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-isothiazolyl, 3-methyl-2-isoxazolyl, 3-methyl-4-oxazolyl,3-methyl-2-pyrrolyl, 3-methyl-2-pyridyl, or m-tolyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-methoxy, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 4-bromo, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is cyclopentyl, cyclopenten-3-yl,cyclopentadien-4-yl; cyclohexyl, or cyclohexen-2-yl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂-R₄ are H, R′ is—(CH₂)_(n)—B, where n is 2, and B is pyridyl, piperazinyl,piperazinonyl, piperidinyl, piperidinonyl, morpholyl, furyl,tetrahydrofuryl, or pyrimidyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ andR₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B is isothiazolyl,isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl, thienyl,furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl,isothiazolinyl, isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, orphenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is trans-3-(2-methylcyclopropyl), R₂ is4-chloro, R₃ and R₄ are H, R′ is —(CH₂)_(n)—B, where n is 2, and B isisothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl, thiazolyl,thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, thiazolinyl,thiazolidinyl, isothiazolinyl, isothiazolidinyl, imidazolinyl,imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-(2-fluoroethyl), and R₄ is H, R′ is —(CH₂)_(n)—B, where n is 2, and Bis isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl, oxazolidinyl,thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl, pyrrolidinyl,thiazolinyl, thiazolidinyl, isothiazolinyl, isothiazolidinyl,imidazolinyl, imidazolyl, pyridyl, or phenyl.

In a still more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is 3-cyclopropyl, R₂ is 4-chloro, R₃ is2-chloro, R₄ is 2-fluoro, R′ is —(CH₂)_(n)—B, where n is 2, and B is3-methyl-2-pyridyl, 3-methyl-2-piperazinyl, 3-methylpiperazin-2-on-1-yl,3-methyl-1-piperidinyl, 3-methyl-2-piperidinonyl, 3-methyl-1-morpholyl,3-methyl-2-furyl, 3-methyl-2-tetrahydrofuryl, or 2-methyl-1-pyrimidyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is methyl, ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is halogen, R₂-R₄ are H, and R′ is methyl,ethyl, isopropyl, or sec-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 1,2-chloropropan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is l-hydroxy-butan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ is bromo, R₂-R₄ are H, and R′ isisopropyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 1,2-dihydroxy-propan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 2-hydroxyethyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R are H, and R′is 1,2-dihydroxybutan-4-yl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are C₁-C₆alkyl, and R′ is 1,2-dihydroxybutan-3-yl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 4-hydroxybutyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1 in which R₁ and R₂ are halogen, R₃ and R₄ are H, andR′ is 3-hydroxypropyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1, where R₁ and R₂ are fused cyclohexyl or fusedcyclopentyl, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIIA-1, where R₁ and R₂ are benzo, R₃ and R₄ are H, and R′ isisopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XIIA-1, where R₁ and R₂, at positions 2 and 3, arefused cyclopentyl, R₃ and R₄ are H, and R′ is isopropyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XIIA-1, where R₁ and R₂, at positions 3 and 4, arebenzo, R₃ and R₄ are H, and R′ is isopropyl, 2-(2-furyl)ethyl,2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention contemplates acompound of formula XIIA-1, where R₁ and R₂, at positions 3 and 4, arebenzo, said benzo bearing fluoro at each ortho position, R₃ and R₄ areH, and R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

Additional contemplated compounds for generic embodiment XIIA-1 areshown in the table below

Cpd # Structure 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

In an additional subgeneric embodiment, this invention provides acompound of formula XIIB-1,

where R₁-R′ are defined as for formula A.

In a more specific embodiment, this invention provides a compound offormula XIIB-1, where R′ is isopropyl, 2-(2-furyl)ethyl, 2-hydroxyethyl,2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIIB-1, where R₁-R₄ are, independently, H, C₁-C₃ alkyl, orhalogen, and R′ is —(CH₂)_(n)—B, where n is 1 or 2, and B is pyridyl,piperazinyl, piperazinonyl, piperidinyl, piperidinonyl, morpholyl,furyl, tetrahydrofuryl, or pyrimidyl.

In another subgeneric embodiment, this invention provides a compound offormula XIIB-2 below,

In a more specific embodiment, this invention provides a compound offormula XIIB-2 where R₁-R₄ are H and R′ is isopropyl, 2-butyl,2-(2-furyl)ethyl, 2-hydroxyethyl, 2,3-dihydroxy-1-propyl, or3,4-dihydroxy-2-butyl.

In another more specific embodiment, this invention provides a compoundof formula XIIB-2, where R₁ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIIB-2, where R₂ is amino, methyl amino, dimethylamino,dimethylaminomethyl, or acetylamino, R₁ and R₂-R₄ are H, and R′ is C₁-C₆alkyl, optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

In another more specific embodiment, this invention provides a compoundof formula XIIB-2, where R₁ is nitro, cyano, methylcarbamoyl,dimethylcarbamoyl, or aminosulfonyl, R₂-R₄ are H and R′ is C₁-C₆ alkyl,optionally substituted with halogen, C₁-C₃ alkoxy, or hydroxy.

Examples of additional embodiments of the aza-substituted type are shownbelow, along with prophetic examples of each. In the first column,non-carbon ring members of T-Z of formula XII are identified.

Generic Structure: Formula XII, where Example X = NXIIB-3

XIIB-3a X and Z = NXIIB-4

XIIB-4a X and T = NXIIB-5

XIIB-5a T = NXIIB-6

XIIB-6a U = NXIIB-7

XIIB-7a X and U = NXIIB-8

XIIB-8a U, X, and Z = NXIIB-9

XIIB-9a U and W = NXIIB-10

XIIB-10a U and Z are NXIIB-11

XIIB-11a X, V, and T = NXIIB-12

XIIB-12a

In additional more specific embodiments, the invention providescompounds according to any of formulas XIIB-1 to XIIB-12, wherein R₁-R₄are all independently halo, halomethyl, methyl, methoxy, ethyl, vinyl,ethynyl, or H, and R₅ is —(CH₂)_(n)—B, where n is 1 or 2, and B isimidazolyl, cyclopentyl, cyclopenten-3-yl, cyclohexyl, cyclohexen-2-yl,phenyl, pyridyl, piperazinyl, piperazinonyl, piperidinyl, piperidinonyl,morpholyl, furyl, tetrahydrofuryl, or pyrimidyl.

In additional more specific embodiments, the invention contemplatescompounds according to any of formulas XIIB-1 to XIIB-12, where R₁ isbromo, R₂-R₄ are all H and R₅ is isopropyl, 2-hydroxyethyl,1-hydroxy-2-propyl, 2,3-dihydroxy-1-propyl, or 3,4-dihydroxy-2-butyl.

In still more specific embodiments, the invention contemplates compoundsaccording to any of formulas XIIB-1 to XIIB-12, where R₁-R₄ are all Hand R₅ is isopropyl or 2,3-dihydroxy-1-propyl.

This invention also contemplates other patterns of aza-substitution andpoly-aza-substitution not depicted in the examples shown above.

EXPERIMENTAL DETAILS Synthesis

Compounds of this invention are prepared according to the schemes below.

I. Synthesis of Contemplated Compounds

The choice of synthetic strategy is not critical to the practice of thisinvention. Suitable approaches include both those in which commerciallyavailable or previously synthesized isothiazoles are modified and thoseinvolving cyclization of a thiocarbamoyl acetamide to form theisothiazole ring system.

Scheme 1 illustrates a reaction of 2-cyanoacetamide with anisothiocyanate to an intermediate, and subsequent ring closure byoxidation followed by amination by heating the cyano compound with anamine (e.g., isopropylamine, 2-amino-propan-1-ol) to provide the amidine4. This general strategy can be used for compounds of formulas II-VI.

More specifically, in step 1 of Scheme 1,2-cyanoacetamide was treatedwith a strong base (e.g., KOH) and then with a substituted phenylisothiocyanate 1 in N,N-dimethylformamide (DMF) at a temperature rangingfrom about −10° C. to 60° C., preferably about 25° C., for a period ofabout 8 to 24 hours, preferably about 16 hours, to produce compound 2.Then, in step 2 of Scheme 1, compound 2 (in the same reaction vessel asstep 1) was treated at about 0° C. with aqueous chloramine solution forabout 12 hours, and compound 3 was isolated.

Alternatively, the reaction mixture of step 1 was concentrated anddiluted with water, followed by acidification with aqueous hydrochloricacid solution. Filtration and washing with water afforded compound 2. Inan organic solvent, preferably ethyl acetate, compound 2 was treatedwith bromine to provide isothiazole 3. In step 3 of Scheme 1, compound 3was agitated with an alkylamine (including a hydroxyalkylamine) inethanol, in a sealed reaction vessel at about 80-120° C., preferablyabout 100° C., for about 16 to 24 hours, preferably 18 hours, to provideamidine 4 in good yield after chromatography.

Scheme 1 includes the synthesis of compounds wherein R₁ is a phenoxy orphenylthio group. In a variation of Scheme 1, a pyridyl, naphthyl, orquinolyl isothiocyanate may be used in place of the phenylisothiocyanate that is illustrated. Compounds in which R₁ is a benzyl,benzoyl, phenylazido, or phenylacetyl group are prepared usingcommercially available precursors such as p-nitro benzophenone, p-nitrodiphenylmethane, and p-nitro diphenylazide. In a variation of Scheme 1,a pyridyl, naphthyl, or quinolyl isothiocyanate may be used in place ofthe phenyl isothiocyanate that is illustrated.

Preparation of Isothiazoles Using 4-substituted Anilines

The p-phenoxy phenylisothiocyanates can be synthesized by condensing theappropriately substituted p-fluoronitrobenzene with a phenol or aniline,as shown below.

General Procedure for 4-substituted Phenols and Anilines

Preparation of Isothiocyanates from Anilines

A mixture comprising a 4-fluoronitrobenzene 6 (0.02 mol), a suitableaniline or phenol 7 (0.022 mol), and potassium carbonate (0.022 mol) in40 ml of anhydrous DMF was heated overnight at 150° C. with stirring.After cooling to room temperature, the reaction mixture was poured into500 ml of ice water and stirred for 30 min. The precipitate wascollected by filtration, washed with water, and dried in vacuo to give a4-substituted nitrobenzene 8. The nitrobenzene 8 was dissolved in100-200 ml of ethanol and stirred for 5-6 hours under hydrogen in thepresence of catalyst 10% Pd—C (50-100 mg), at atmospheric pressure andambient temperature. The catalyst was removed by filtration, and thefiltrate was concentrated to dryness to give the crude substitutedaniline 9, which was used for the next step without furtherpurification.

Method 1: The appropriate aniline 10 (30 mmol) was added to a biphasicmixture of CHCl₃ and saturated aqueous NaHCO₃ (1:1, v/v, 247 ml),followed by dropwise addition at room temperature, with stirring, of asolution of thiophosgene (30 mmol) in dichloromethane (20 ml). Themixture was stirred vigorously at room temperature for 1 hour. Thebottom layer of the mixture was separated, and the aqueous layer wasextracted twice with CHCl₃. The combined organic solution was washedwith water, dried over MgSO₄, and evaporated to give isocyanate 11 as ayellow solid, which was used for the next step without furtherpurification.

Method 2: To a solution of aniline (30 mmol) and DBU (60 mmol) in 60 mlof anhydrous dichloromethane, a solution of thiophosgene (30 mmol) in 20ml of dry dichloromethane was added dropwise with stirring at roomtemperature over 30 minutes. The reaction mixture was diluted with 200ml of chloroform and washed with 1N HCl solution (300 ml×2) and water(300 ml) respectively. The chloroform solution was dried over anhydroussodium sulfate, and the solvent was evaporated in vacuo. The residue waspurified by silica gel column to give pure isothiocyanates.

(3) Preparation of Isothiazoles (see Scheme 1)3-Hydroxy-5-phenylamino-isothiazol-4-carbonitrile

Method 1: To a cooled suspension of finely ground potassium hydroxide(0.337 g, 6 mmol) in DMF (8 ml) was added cyanoacetamide (0.505 g, 6mmol) followed by addition of 4-methoxyphenyl isothiocyanate (0.83 ml, 6mmol). The reaction mixture was stirred at room temperature for 24 hoursand treated with aqueous chloramine (30 ml) at 0° C. The mixture wasfurther stirred at room temperature for 12 hours, and evaporated to givea residue, which was partitioned between water and ethyl acetate. Theaqueous layer was washed twice with ethyl acetate, then cooled to 0° C.and acidified with 1N HCl solution to about pH-3. The precipitate wasfiltered and washed with water and dried in vacuo to afford a yellowpowder (0.95 g, 73%).

Method 2: Condensation of isothiocyanate with 2-cyanoacetamide:Procedure 1: To a cooled suspension of finely ground potassium hydroxide(0.337 g, 6 mmol) in DMF (8 ml) was added cyanoacetamide (0.505 g, 6mmol), followed by addition of 4-methoxyphenyl isothiocyanate (0.83 ml,6 mmol). The reaction mixture was stirred at room temperature for 16hours and concentrated to give a syrup, which was diluted with water andacidified with 1 N aqueous HCl solution. The suspension was filtered,and the solid was washed with water and dried in vacuo. Procedure 2: Toa solution of potassium tert-butoxide (20 mmol) in 20 ml of anhydrousTHF was added 2-cyanoacetamide (20 mmol). The mixture was cooled to 5°C. and a solution of isothiocyanates (20 mmol) in 5 ml of dry THF wasadded dropwise with stirring under argon. After 15 min with stirring at5° C., the reaction mixture was warmed to room temperature and stirredfor another 1 h. The reaction mixture was poured into 1000 ml of icewater and neutralized with 2% HCl solution to pH<7. The solid wasfiltered and washed with water. After drying in vacuo, the crude productwas obtained and it is pure enough for next step (Yield: 72-97%).

Cyclization: The above dried solid was dissolved in ethyl acetate (30ml), and a solution of bromine (0.31 ml, 6 mmol) in ethyl acetate (25ml) was added drop wise into the mixture. After 1 hour of stirring atroom temperature, the reaction mixture was filtered, and the solid waswashed with ethyl acetate and dried in vacuo to afford a yellow powder(0.86 g, 66%).

Preparation of 5-benzimidazole, oxazole, thiazole, and isothiazolecarboxamidines

The 2-(4-aminophenyl)benzoxazole, benzothiazole, or benzimidazole wasprepared by condensation of the appropriate aniline derivative withp-amino benzoic acid using polyphosphoric acid. The product wasconverted to the corresponding isothiocyanate with thiophosgene andsubsequently condensed with cyanoacetamide to form the thiocarbamoylcyanoacetamide. Treatment with bromine afforded the cyano hydroxythiazole, which was converted to carboxamidine by treatment with theappropriate amide, as shown above.

PREPARATION OF EXAMPLES

A typical procedure for synthesis of isothiazole carboxamidines is thatemployed for synthesis of3-hydroxy-N-isopropyl-5-(4-phenoxyphenylamino)-isothiazole-4-carboxamidine:

A mixture of 3-hydroxy-4-cyano-5-(4-phenoxyphenylamino)isothiazole (5 g)and isopropylamine (25 ml) in 250 ml of ethanol was placed into ahigh-pressure reaction equipment and heated to 120° C. with stirring for9 hours. The reaction mixture was cooled to room temperature, and thesolvent was removed under vacuum. The residue was treated with 500 ml ofdiethyl ether, and the precipitates were filtered and washed withdiethyl ether. The filtrates were evaporated to dryness, and the residuewas purified by silica gel column chromatography (chloroform/methanol,60:1) to give 3.51 g (59%) of product as a foam, which wasrecrystallized from methanol to give yellowish crystals. MS: 368; ¹H NMR(DMSO-d6): 10.44 (brs, 1/2H, NH, D₂O exchangeable), 9.81 (brs, 1/2H, NH,D₂O exchangeable), 9.51 (brs, 1/2H, NH, D₂O exchangeable), 9.15 (brs,1/2H, NH, D₂O exchangeable), 8.36 (s, 1H, OH, D₂O exchangeable), 7.87(brs, 1/2H, NH, D₂O exchangeable), 7.66 (brs, 1/2H, NH, D₂Oexchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H, J=7.5 Hz, ArH),6.96 (m, 6H, ArH), 3.85 (m, 1H, CH), 1.20 (d, 6H, J=6.3 Hz, 2×CH₃).

The isothiazole carboxamidines listed in table 2 were synthesized by theprocedure above. Most reactions were run using 100-200 mg of startingmaterials in about 20-30 ml of ethanol at 90° C. for 24-48 hours. Inmost cases products were purified by silica gel column chromatography.Some compounds were purified by preparative HPLC or TLC.

N-Cyclohexylmethyl-3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carboxamidine

To a suspension of 85% powdered KOH in 20 ml DMF was added 1.74 g ofcyanoacetamide at room temperature. The solution was stirred at roomtemperature for 15 minutes and then cooled in a water bath at roomtemperature. To this solution 4.7 g of 3-phenoxy-phenyl isothiocyanatewas added dropwise. The solution exothermed slightly with the internaltemperature rising to 28° C. during the addition. The solution wasstirred at room temperature for 16 h, then diluted with 150 ml water andextracted with ethyl acetate to remove small amounts of startingmaterial and by-products. The aqueous layer was isolated and acidifiedwith 1N HCl to pH 1 with vigorous stirring. The resulting tanprecipitate was filtered, washed with water, and dried for 16 hours in avacuum oven to afford 4.66 g of2-cyano-2-(3-phenoxy-phenylthiocarbamoyl)-acetamide.

The product of the previous step was suspended in 100 ml ethyl acetateand stirred vigorously. A solution of 767 μl Br₂ in 25 ml ethyl acetatewas added via addition funnel over 30 minutes. After 1.5 h, saturatedaqueous NaHCO₃ was added, and the resulting biphasic mixture was stirredfor 30 minutes. The mixture was filtered and washed with ethyl acetate,followed by water and dried in vacuo to afford 2.75 g (43%) of3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carbonitrile as a tansolid. To a suspension of 190 mg of this material in 10 ml ethyl alcoholin a 40 ml Teflon-lined screw-thread vial was added 500 μl cyclohexylmethylamine and heated to 80° C. After 18 h, the reaction was cooled andthe solvent evaporated. The residue was purified by preparative HPLC toafford 26 mg (10%) ofN-cyclohexylmethyl-3-hydroxy-5-(3-phenoxy-phenylamino)-isothiazole-4-carboxamidineas a tan solid. ¹H NMR ((CD₃)₂SO) δ 0.969 m 2H, 1.161 m 3H, 1.718-1.510m 6H, 3.109 t 2H J=6.3 Hz, 6.473 s 1H, 6.633 dd 1H J=2.1 and 7.8 Hz,6.698 dd 1H J=1.2 and 7.8 Hz, 7.014 d 2H J=7.8 Hz, 7.130 t 1H J=7.5 Hz,7.276 t 1H, J=7.2 Hz, 7.381 t 2H J=8.1 Hz, 7.691 bs 1/2H, 8.416 s 1H,9.099 bs 1/2H, 9.745 bs 1/2H, 10.566 bs 1/2H. MS m/z. 423 (M+1), 421(M−1).

Preparation of5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-isopropyl-isothiazole-4-carboxamidineand5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine

1-(2,5-Dichloro-phenoxy)-2-fluoro-4-nitro-benzene

A mixture of 3,4-difluoronitrobenzene (3.2 g, 0.02 mol),2,5-dichlorophenol (3.59 g, 0.022 mol), and potassium carbonate (3.0 g,0.022 mol) in 25 ml of anhydrous DMF was heated to 150° C. with stirringovernight. After cooling to room temperature, the reaction mixture waspoured into 500 ml of ice water and stirred for 30 min. The precipitateswere collected by filtration, washed with water, and dried in vacuo togive 5.72 g (94.7%) of crude product.

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamine

A mixture of 1-(2,5-dichloro-phenoxy)-2-fluoro-4-nitro-benzene (0.5 g,1.7 mmol) and tin chloride (1.57 g, 8.3 mmol) in 30 ml of anhydrousethanol was heated to 70° C. under argon and stirred for 4 hours. Thesolution was allowed to cool and then poured into ice. The solution wasmade slightly basic (pH 7-8) by addition of saturated aqueous sodiumbicarbonate solution, then extracted with ethyl acetate. The organicphase was thoroughly washed with brine and dried treated with anhydroussodium sulfate. Evaporation of the solvent left a yellow oily productwhich was used for the next step without further purification.

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylisothiocyanate

4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamine (1.36 g, 5 mmol) wasdissolved in 150 ml of chloroform and 100 ml of saturated aqueous sodiumbicarbonate was added. To this biphasic mixture was added dropwise asolution of thiophosgene (0.39 ml, 5 mmol) in 30 ml of chloroform atroom temperature with vigorous stirring. The mixture was stirredvigorously for 1 hour at room temperature. The bottom layer of themixture was separated, and the aqueous layer was extracted twice withCHCl₃. The combined organic solution was washed with water, dried overMg₂SO₄ and evaporated to give 1.53 g (97.4%) of crude product used fornext step without further purification.

2-Cyano-2-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylthiocarbamoyl]-acetamide

To a solution of potassium tert-butoxide (0.6 g, 5.36 mmol) in 10 ml ofanhydrous THF was added 2-cyanoacetamide (0.45 g, 5.36 mmol) underargon. The mixture was cooled to 5° C. and added dropwise to a solutionof 4-(2,5-dichloro-phenoxy)-3-fluoro-phenylisothiocyanate (1.53 g, 4.87mmol) in 5 ml of dry THF with stirring under argon. After 15 min ofstirring at 5° C., this reaction mixture was warmed to room temperatureand stirred for another 2 h. The reaction mixture was poured into 200 mlof ice water with stirring and acidified with 10% HCl. The solid wasfiltered and washed with water. After drying in vacuo, the crude product(1.6 g, 82.5%) was obtained in sufficient purity for the next step.

5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile

2-Cyano-2-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylthiocarbamoyl]-acetamide(1.6 g, 4 mmol) was dissolved in anhydrous ethyl acetate (60 ml) and asolution of bromine (0.2 ml, 4 mmol) in anhydrous ethyl acetate (10 ml)was added dropwise into the mixture with stirring at room temperature.After addition, the reaction mixture was stirred for another 3 hours.The precipitate was filtered and the solid was washed with ethyl etherand suspended in a saturated sodium bicarbonate with stirring for 10min. The solid was filtered, then washed with water and dried in vacuoto afford a white powder.

Exemplary Physical Data5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-isopropyl-isothiazole-4-carboxamidine

A mixture of5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile(0.2 g) and isopropylamine (5 ml) in 20 ml of ethanol was placed into ahigh-pressure reaction apparatus and heated to 100° C. overnight. Thereaction mixture was cooled to room temperature, and the solvent wasremoved in vacuo. The residue was chromatographed by silica gel column(chloroform/methanol, 40:1) to give the desired product as a lightyellow solid. MS: 454; ¹H NMR (DMSO-d₆, 300 MHz): δ 10.28 (brs, 1/2H,NH, D₂O exchangeable), 9.62 (brs, 1H, NH, D₂O exchangeable), 9.31 (brs,1/2H, NH, D₂O exchangeable), 8.57 (s, 1H, OH, D₂O exchangeable), 7.88(brs, 1H, NH, D₂O exchangeable), 7.61 (d, 1H, J=8.7 Hz, ArH), 7.22 (dd,1H, J=2.1, 8.7 Hz, ArH), 7.16 (t, 1H, J=8.7 Hz, ArH), 6.99 (dd, 1H,J=2.1, 12.6 Hz, ArH), 6.88 (d, 1H, J=2.1 Hz, ArH), 6.83 (dd, 1H, J=2.1,8.7 Hz, ArH), 3.85 (m, 1H, CH), 1.20 (d, 6H, J=6.3 Hz, 2×CH₃).

5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine

A mixture of5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile(0.2 g) and DL-2-amino-1-propanol (0.7 g) in 20 ml of ethanol was placedin a high-pressure reaction equipment and heated to 100° C. overnight.The reaction mixture was cooled to room temperature and the solvent wasremoved in vacuo. The residue was chromatographed by silica gel column(chloroform/methanol, 25:1) to give the desired product as a lightyellow solid. MS: 470; ¹H NMR (DMSO-d₆, 300 MHz): δ 10.60 (brs, 1/2H,NH, D₂O exchangeable), 9.69 (brs, 1/2H, NH, D₂O exchangeable), 9.22(brs, 1/2H, NH, D₂O exchangeable), 8.55 (s, 1H, OH, D₂O exchangeable),7.91 (brs, 1/2H, NH, D₂O exchangeable), 7.70 (brs, 1/2H, NH, D₂Oexchangeable), 7.61 (d, 1H, J=8.7 Hz, ArH), 7.22 (dd, 1H, J=2.1, 8.7 Hz,ArH), 7.16 (t, 1H, J=8.7 Hz, ArH), 6.99 (dd, 1H, J=2.1, 12.6 Hz, ArH),6.88 (d, 1H, J=2.1 Hz, ArH), 6.83 (dd, 1H, J=2.1, 8.7 Hz, ArH), 5.09(brs, 1H, OH), 3.80 (m, 1H, CH), 3.49 (m, 1H, CH). 3.44 (m, 1H, CH),1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-(3-hydroxy-2,2-dimethyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.64 (broad s, 1/2H), 9.81 (broad s, 1/2H),9.15 (broad s, 1H), 8.38 (broad s, 1H), 7.64 (broad s, 1/2H), 7.40(apparent d, J=7.2 Hz, 2H), 7.14 (apparent t, J=7.2 Hz, 1H), 7.01 (s,6H), 4.90 (broad s, 1H), 3.24 (s, 2H), 3.18 (s, 2H), 0.941 (s, 6H). MS(EI) m/z 413 (M+1)⁺.

3-Hydroxy-N-(4-hydroxy-butyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 11.21 (broad s, 1/2H), 10.59 (broad s,1/2H), 10.38 (broad s, 1/2H), 9.92 (broad s, 1/2H), 9.15 (s, 1H), 8.66(broad s, 1/2H), 8.48 (broad s, 1/2H), 8.17 (t, J=8.4 Hz, 2H), 7.89 (t,J=7.2 Hz, 1H), 7.77 (d, J=5.4 Hz, 1H), 7.76 (s, 5H), 5.30 (t, J=4.8 Hz,1H), 4.23 (q, J=6.0 Hz, 2H), 4.20-4.08 (m, 2H), 2.41-2.28 (m, 4H).

3-Hydroxy-N-(2-hydroxy-ethyl)-5-[4-(pyrimidin-5-yloxy)-phenylamino]-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 11.62 (broad s, 1/2H), 9.86 (broad s, 1/2H),9.72 (broad s, 1/2H), 9.22 (broad s, 1/2H), 9.01 (s, 1H), 8.62 (s, 2H),8.44 (s, 1H), 7.91 (broad s, 1/2H), 7.68 (broad s, 1/2H), 7.15 (d, J=8.7Hz, 2H), 7.05 (t, J=9.0 Hz, 2H), 5.05 (t, J=5.1 Hz, 1H), 3.64 (apparentd, J=5.1 Hz, 2H), 3.38 (apparent t, J=5.7 Hz, 2H).

N-tert-Butyl-3-hydroxy-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.93 (broad s, 1/2H), 10.15 (broad s,1/2H), 9.94 (broad s, 1/2H), 9.48 (broad s, 1/2H), 8.47 (broad s, 1H),7.41 (t, J=8.1 Hz, 2H), 7.14 (t, J=7.2 Hz, 1H), 7.02 (d, J=5.4 Hz, 2H),7.01 (s, 5H), 1.45 (s, 9H). MS (EI) m/z 381 (M−1)⁺.

3-Hydroxy-N-(4-hydroxy-cyclohexyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

¹H NMR (DMSO-d₆, 300 MHz) δ 10.56 (broad s, 1/2H), 9.83 (broad s, 1/2H),9.61 (broad s, 1/2H), 9.18 (broad s, 1/2H), 8.41 (broad s, 1H), 7.98(broad s, 1/2H), 7.73 (broad s, 1/2H), 7.41 (t, J=7.8 Hz, 2H), 7.14 (t,J=7.5 Hz, 1H), 7.01 (d, J=5.4 Hz, 1H), 7.00 (s, 5H), 4.66 (d, J=4.5 Hz,1H), 3.59-3.53 (m, 2H), 2.00 (broad s, 2H), 1.85 (broad s, 2H), 1.34(broad s, 4H). MS (EI) m/z 423 (M−1)⁺.

3-Hydroxy-N-(2-hydroxy-1-methyl-ethyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR (DMSO-d6): 10.60 (brs, 1/2H, NH, D₂O exchangeable), 9.83(brs, 1/2H, NH, D₂O exchangeable), 9.61 (brs, 1/2H, NH, D₂Oexchangeable), 9.15 (brs, 1/2H, NH, D₂O exchangeable), 8.33 (s, 1H, OH,D₂O exchangeable), 7.85 (brs, 1/2H, NH, D₂O exchangeable), 7.58 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.78 (m, 1H, CH), 3.47 (m, 1H, CH), 3.43 (m, 1H, CH),1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-[(S)-2-hydroxy-1-methyl-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR (DMSO-d6): 10.60 (brs, 1/2H, NH, D₂O exchangeable), 9.84(brs, 1/2H, NH, D₂O exchangeable), 9.60 (brs, 1/2H, NH, D₂Oexchangeable), 9.17 (brs, 1/2H, NH, D₂O exchangeable), 8.33 (s, 1H, OH,D₂O exchangeable), 7.85 (brs, 1/2H, NH, D₂O exchangeable), 7.58 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.78 (m, 1H, CH), 3.47 (m, 1H, CH), 3.42 (m, 1H, CH),1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-[(R)-2-hydroxy-1-methyl-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR (DMSO-d6): 10.60 (brs, 1/2H, NH, D₂O exchangeable), 9.84(brs, 1/2H, NH, D₂O exchangeable), 9.59 (brs, 1/2H, NH, D₂Oexchangeable), 9.17 (brs, 1/2H, NH, D₂O exchangeable), 8.34 (s, 1H, OH,D₂O exchangeable), 7.85 (brs, 1/2H, NH, D₂O exchangeable), 7.59 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.06 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.78 (m, 1H, CH), 3.48 (m, 1H, CH), 3.42 (m, 1H, CH),1.15 (d, 3H, J=6.3 Hz, CH₃).

3-Hydroxy-N-(1-hydroxymethyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR (DMSO-d6): 10.61 (brs, 1/2H, NH, D₂O exchangeable), 9.83(brs, 1/2H, NH, D₂O exchangeable), 9.62 (brs, 1/2H, NH, D₂Oexchangeable), 9.15 (brs, 1/2H, NH, D₂O exchangeable), 8.34 (s, 1H, OH,D₂O exchangeable), 7.83 (brs, 1/2H, NH, D₂O exchangeable), 7.56 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H,CHMe), 1.50 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-[(S)-1-hydroxymethyl-propyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR (DMSO-d6): 10.59 (brs, 1/2H, NH, D₂O exchangeable), 9.82(brs, 1/2H, NH, D₂O exchangeable), 9.61 (brs, 1/2H, NH, D₂Oexchangeable), 9.16 (brs, 1/2H, NH, D₂O exchangeable), 8.33 (s, 1H, OH,D₂O exchangeable), 7.83 (brs, 1/2H, NH, D₂O exchangeable), 7.56 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H,CHMe), 1.49 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-[(R)-1-hydroxymethyl-propyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 398; ¹H NMR (DMSO-d6): 10.59 (brs, 1/2H, NH, D₂O exchangeable), 9.83(brs, 1/2H, NH, D₂O exchangeable), 9.60 (brs, 1/2H, NH, D₂Oexchangeable), 9.15 (brs, 1/2H, NH, D₂O exchangeable), 8.33 (s, 1H, OH,D₂O exchangeable), 7.83 (brs, 1/2H, NH, D₂O exchangeable), 7.58 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.62 (m, 1H, CHN), 3.47 (m, 2H, CH₂O), 1.62 (m, 1H,CHMe), 1.49 (m, 1H, CHMe), 0.90 (t, 3H, J=7.2 Hz, CH₃).

3-Hydroxy-N-(1-hydroxymethyl-2-methyl-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 412; ¹H NMR (DMSO-d6): 10.62 (brs, 1/2H, NH, D₂O exchangeable), 9.81(brs, 1/2H, NH, D₂O exchangeable), 9.68 (brs, 1/2H, NH, D₂Oexchangeable), 9.15 (brs, 1/2H, NH, D₂O exchangeable), 8.36 (s, 1H, OH,D₂O exchangeable), 7.82 (brs, 1/2H, NH, D₂O exchangeable), 7.56 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 4.97 (t, 1H, J=5.1 Hz, OH, D₂Oexchangeable), 3.58 (m, 1H, CHN), 3.49 (m, 2H, CH₂O), 1.96 (m, 1H,CHMe), 1.49 (m, 1H, CHMe), 0.92 (d, 6H, J=6.9 Hz, 2×CH₃).

3-Hydroxy-N-(2-hydroxy-propyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 384; ¹H NMR (DMSO-d6): 10.62 (brs, 1/2H, NH, D₂O exchangeable), 9.82(brs, 1/2H, NH, D₂O exchangeable), 9.67 (brs, 1/2H, NH, D₂Oexchangeable), 9.13 (brs, 1/2H, NH, D₂O exchangeable), 8.31 (s, 1H, OH,D₂O exchangeable), 7.82 (brs, 1/2H, NH, D₂O exchangeable), 7.56 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.00 (d, 1H, J=4.8 Hz, OH, D₂Oexchangeable), 3.82 (m, 1H, CH), 3.24 (m, 1H, CH), 3.12 (m, 1H, CH),1.11 (d, 3H, J=6.0 Hz, CH₃).

3-Hydroxy-N-(trans-2-hydroxy-cyclohexyl)-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 424; ¹H NMR (DMSO-d6): 10.61 (brs, 1/2H, NH, D₂O exchangeable), 9.74(brs, 1/2H, NH, D₂O exchangeable), 9.60 (brs, 1/2H, NH, D₂Oexchangeable), 9.08 (brs, 1/2H, NH, D₂O exchangeable), 8.34 (s, 1H, OH,D₂O exchangeable), 7.74 (brs, 1/2H, NH, D₂O exchangeable), 7.48 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.95 (m, 6H, ArH), 5.08 (d, 1H, J=4.8 Hz, OH, D₂Oexchangeable), 3.34 (m, 2H, 2×CH), 1.88 (m, 2H, CH₂), 1.63 (m, 2H, CH₂),1.27 (m, 4H, 2×CH₂).

3-Hydroxy-N-[(S)-1-hydroxymethyl-3-methyl-butyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 426; ¹H NMR (DMSO-d6): 10.49 (brs, 1/2H, NH, D₂O exchangeable), 9.81(brs, 1/2H, NH, D₂O exchangeable), 9.50 (brs, 1/2H, NH, D₂Oexchangeable), 9.15 (brs, 1/2H, NH, D₂O exchangeable), 8.34 (s, 1H, OH,D₂O exchangeable), 7.85 (brs, 1/2H, NH, D₂O exchangeable), 7.57 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (t, 1H,J=7.5 Hz, ArH), 6.94 (m, 6H, ArH), 4.99 (t, 1H, J=4.8 Hz, OH, D₂Oexchangeable), 3.76 (m, 1H, CHN), 3.45 (m, 1H, CH₂O), 3.40 (m, 1H,CH₂O), 1.64 (m, 1H, CHMe₂), 1.41 (t, 2H, CH₂), 0.90 (d, 3H, J=6.6 Hz,CH₃), 0.87 (d, 3H, J=6.6 Hz, CH₃).

3-Hydroxy-N-[2-hydroxy-2-(3-hydroxy-phenyl)-ethyl]-5-(4-phenoxy-phenylamino)-isothiazole-4-carboxamidine

MS: 462; ¹H NMR (DMSO-d6): 10.65 (brs, 1/2H, NH, D₂O exchangeable), 9.76(brs, 1/2H, NH, D₂O exchangeable), 9.37 (brs, 1/2H, NH, D₂Oexchangeable), 9.14 (brs, 1/2H, NH, D₂O exchangeable), 8.31 (s, 1H, OH,D₂O exchangeable), 7.84 (brs, 1/2H, NH, D₂O exchangeable), 7.57 (brs,1/2H, NH, D₂O exchangeable), 7.35 (t, 2H, J=7.5 Hz, ArH), 7.08 (m, 2H,J=7.5 Hz, ArH), 6.94 (m, 6H, ArH), 6.85 (m, 2H, ArH), 6.64 (d, 1H, J=7.5Hz, ArH), 5.76 (brs, 1H, OH, D₂O exchangeable), 4.69 (brs, 1H, OH, D₂Oexchangeable), 4.12 (m, 1H, CH), 3.15 (d, 2H, J=4.2 Hz, CH₂).

Similar procedures can be used in the synthesis ofN-2-(2-tetrahydrofuryl)ethyl-3-hydroxy-5-[4-(2,5-Dichloro-phenoxy)-3-fluoro-phenylamino]-isothiazole-4-carboxamidineandN-2-(4-methylpiperazinyl)ethyl-3-hydroxy-5-[4-(2,5-dichloro-phenoxy)-3-fluoro-phenylamino]-isothiazole-4-carboxamidine,as shown below.

The scheme below shows alternative syntheses for compounds of thisinvention in which R′ includes a cyclic moiety.

The following synthetic procedure is provided as an example of synthesisscheme for compounds of formula VII.

4-Isothiocyanato-benzoic acid t-butyl ester 2: To4-amino-t-butyl-benzoate 1, (25.0 g., 129.4 mmol) in a stirred biphasicmixture of CHCl₃ (250 ml) and saturated NaHCO₃ solution (100 ml) in anice bath, thiophosgene (9.9 ml, 129.4 mmol) was added dropwise. Afteraddition of thiophosgene stirring at room temperature was continued for90 min. The organic layer was washed with water, dried over anhydrousNa₂SO₄, and further purified by column chromatography to provide 28.3 g.of 4-isothiocyanato-benzoic acid, t-butyl ester 2.

4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3: To28.3 g., 120.4 mmol of 4-isothiocyanato-benzoic acid t-butyl ester 2 inDMF (200 ml), KOH (6.74 g., 120.4 mmol) and cyanoacetamide (10.21 g.,120.4 mmol) were added. The reaction mixture was stirred at roomtemperature for 16 hours, then acidified with 1N HCl. The precipitateobtained was filtered, washed with water, and dried under vacuum, toprovide 32.10 g. of 4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acidt-butyl ester 3.

4-(4-Cyano-3-hydroxy-isothiazole)-benzoic acid 4: To4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3(32.10 gm, 100.36 mmol) in EtOAc (250 ml), Br₂ (5.2 ml, 100.36 mmol) wasadded slowly. The reaction mixture was kept stirring at room temperaturefor 2 hrs. The precipitate obtained was filtered and washed withsaturated NaHCO₃ solution and dried under vacuum to provide 31 g. of4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4.

5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile5: To 1.0 g. 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4 (3.82mmol) in DMF (30 ml) were added DMAP (dimethylaminopyridine)(0.46 gm,3.82 mmol), EDC (1-ethyl-3,3′-dimethylaminopropyl carbodiimide HCl)(0.732 gm, 3.82 mmol) and indoline (1.28 gm, 3.82 mmol). The reactionmixture was kept stirring at room temperature for 16 h, concentrated todryness, and purified by column chromatography to provide 1.08 gm of5-[4-(2,3-Dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile5.

5-[4-(2,3-dihydro-indole-3-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine6: To5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile5 (0.362 gm, 1 mmol) in 10 ml anhydrous EtOH was added(2-amino-propan-1-ol (0.375 gm, 5 mmol). The reaction mixture wasmaintained at 80° C. for 16 h. with stirring, then concentrated todryness and purified by column chromatography to provide5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine6.

A typical synthetic scheme for compounds of formula VIII is shown below.

Compounds of formulas IX and X are prepared by standard syntheticprocedures that are analogous with those employed for compounds offormulas II-VIII.

A typical synthesis scheme for compounds of formula XI is illustrated bythe procedure for a 5-(meta-indolecarbonylaryl amino isothizoleamidine):

Synthesis scheme for a 5-(meta-dihydroindolecarbonylaryl aminoisothiazole amidine):

Example:5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine6.

4-isothiocyanato-benzoic acid t-butyl ester 2: t-Butyl-4-aminobenzoate1, (25.0 gm, 129.4 mmol) was taken into CHCl₃ (250 ml) and saturatedNaHCO₃ (100 ml) in ice bath. To the stirred mixture thiophosgene (9.9ml, 129.4 mmol) was added dropwise, and stirring continued for another90 min. at room temperature after addition was complete. The organiclayer was washed with water, dried over Na₂SO₄, and further purified bycolumn chromatography to provide 28.3 gm of 4-isothiocyanato-benzoicacid t-butyl ester 2.

4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3:4-Isothiocyanato-benzoic acid t-butyl ester 2 (28.3 gm, 120.4 mmol) wastaken into DMF (200 ml). To this KOH (6.74 gm, 120.4 mmol) andcyanoacetamide (10.21 gm, 120.4 mmol) were added. The reaction mixturewas stirred at room temperature for 16 h. The reaction mixture wasacidified with 1N HCl, the precipitate obtained was filtered, washedwith water, and dried under vacuum, to provide 32.10 gm of4-(2-Carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3.

4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4:4-(2-carbamoyl-2-cyano-thioacetylamino)-benzoic acid t-butyl ester 3(32.10 gm, 100.36 mmol) was taken into EtOAc (250 ml) and to this Br₂(5.2 ml, 100.36 mmol) was added slowly. Reaction mixture was stirred atroom temperature for 2 h. The precipitate obtained was filtered andwashed with saturated NaHCO₃ and dried under vacuum to provide 31 gm of4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4.

5-[3-(3-(1H-indole-1-carbonyl)phenylamino]-3-hydroxyisothiazole-4-carbonitrile5: 4-(4-cyano-3-hydroxy-isothiazole)-benzoic acid 4 (1.0 gm, 3.82 mmol)was taken into DMF (30 ml). To this solution DMAP (0.46 gm, 3.82 mmol),EDC (0.732 gm, 3.82 mmol) and indoline (1.28 gm, 3.82 mmol) were added.The reaction mixture was stirred at room temperature for 16 h.,concentrated to dryness, and purified by column chromatography toprovide 1.08 gm of5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-isothiazole-4-carbonitrile5.

5-[3-(3-(1H-indole-1-carbonyl)phenylamino]-3-hydroxy-N-(1-hydroxypropan-2-yl)isothiazole-4-carboximidamide6:5-[3-(3-(1H-indole-1-carbonyl)phenylamino]-3-hydroxyisothaizole-4-carbonitrile5: (0.362 gm, 1 mmol) was taken into anhydrous EtOH (10 ml) and to this2-amino-propan-1-ol (0.375 gm, 5 mmol) was added. The reaction mixturewas stirred at 80° C. for 16 h., then concentrated to dryness andpurified by column chromatography to provide5-[4-(2,3-dihydro-indole-1-carbonyl)-phenylamino]-3-hydroxy-N-(2-hydroxy-1-methyl-ethyl)-isothiazole-4-carboxamidine6.

Biological Data

Selected compounds were used in various assays to evaluate inhibitoryactivity of the compounds according to the inventive subject matter, andexperimental procedures and results are indicated in tables below,where, unless otherwise indicated, “A” denotes inhibitory concentrationsof 1 nM-100 nM, “B” denotes inhibitory concentrations of 100 nM-500 nM,and “C” denotes inhibitory concentrations of greater than 500 nM(hydroxy groups in the structures of the table below are denoted assingle bonded oxygen as the structures were generated in “hide protonview”).

Generation of IC50 Data

Materials and preparation of reagents: Human GST-MEK1 and theconstitutively active allele GST-MEK1^(CA) (harboring the mutationsSer218Asp and Ser222Asp) were subcloned into the yeast expression vectorpGEM4Z (Promega, Madison, Wis.) from the wild type human MEK1 cDNA.GST-MEK1^(CA) was expressed in Escherichia coli and partially purifiedusing Glutathione Sepharose 4B affinity resin (Amersham PharmaciaBiotech, Piscataway, N.J.). The ERK2 allele was subcloned fromMAPK2/Erk2 cDNA (wild type) in pUSEamp (Upstate Biotechnology, Inc.,Waltham, Mass.) into the vector pET21a (Novagen, Madison, Wis.)resulting in an N-terminal histidine-tagged mouse ERK2 allele. ERK2 wasexpressed and purified to homogeneity [Zhang, 1993 #33]. Myelin basicprotein (MBP) was purchased from Gibco BRL (Rockville, Md.). EasyTidesadenosine 5′-triphosphate (ATP) ([γ-³³P]) (NEN Perkin Elmer, Wellesley,Mass.) was the source of radiolabel for all kinase reactions. ActivatedRaf-1 (truncated) and activated MAPKinase 2/ERK2 were purchased fromUpstate, Inc. (Lake Placid, N.Y.). 4-20% Criterion Precast gels werepurchased from Bio-Rad (Hercules, Calif.).

Determination of enzymatic activity: Compounds were diluted fromdimethylsulfoxide (DMSO) stocks into 1×HMNDE (20 mM HEPES pH 7.2, 1 mMMgCl₂, 100 mM NaCl, 1.25 mM DTT, 0.2 mM EDTA). A typical 25-microliterassay contained 0.002 nanomoles MEK1^(CA), 0.02 nanomoles ERK2, 0.25nanomoles MBP, 0.25 nanomoles unlabeled ATP, and 0.1 μCi [γ³³P] ATP. Thescreening assay essentially comprised four additions. Five μl of dilutedcompound were dispensed to 96-well assay plates. Ten μl of 2.5× enzymecocktail (MEK1^(CA) and ERK2 only) were then added to each well followedby a pre-incubation for 30 minutes at ambient temperature. Ten μl of2.5× substrate cocktail (labeled and unlabeled ATP plus MBP) were thenadded, followed by incubation for 60 minutes at ambient temperature.Finally, 100 μl of 10% trichloroacetic acid (TCA) were added andincubated for 30 minutes at room temperature to halt the reaction andprecipitate radiolabeled protein products. Reaction products wereharvested on glass fiber 96 well filter plates prewetted with water and1% pyrophosphate. The filter plate was then washed 5 times with water.Water was displaced by absolute ethanol and the plate was allowed to airdry for 30 minutes at room temperature. A back seal was applied manuallyand 40 μl of scintillation cocktail were dispensed to each well. A topseal was applied and the plate was counted in the TopCount for twoseconds per well.

Generation of EC50 Data

Effects of compounds in the cell were determined by Western blotting forphosphorylated ERK. MDA-MB-231 breast cancer cells were plated in a 48well plate at 20,000 cells per well and grown in a 37° humidified CO₂incubator. The following day, the growth media (DMEM+10% fetal bovineserum) was removed and replaced with starve media (DMEM+0.1% fetalbovine serum). Cells were incubated in the starve media for sixteenhours and then treated with a range of compound concentrations forthirty minutes. After incubation with compound, cells were stimulatedwith 100 ng/ml EGF for five minutes. The cells were then lysed andanalyzed by Western blot using a monoclonal antibody raised tophosphorylated ERK. The signal was amplified using a secondary antibodyconjugated to a near −IR dye and detected on a Licor Odyssey scanner.The intensity of signal was quantitated and this data was used togenerate dose response curves and EC50 calculations.

TABLE 1 Biological Activity of Compounds of Formula I # Structure AvgIC50 1

B 2

B 3

C 4

B 5

B 6

A 7

B 8

C 9

A 10

A 11

A 12

A 13

A 14

B 15

A 16

A 17

B 18

B 19

A 20

B 21

A 22

A 23

A 24

C 25

A 26

C 27

B 28

A 29

B 30

B 31

A 32

A 33

A 34

B 35

B 36

B 37

A 38

B 39

A 40

A 41

B 42

A 43

A 44

C 45

A 46

A 47

A 48

A 49

A 50

A 51

A 52

A 53

B 54

B 55

B 56

C 57

C 58

C 59

C 60

C 61

B 62

C 63

B 64

C 65

B 66

C 67

C 68

C 69

C 70

B 71

C 72

C 73

B 74

C 75

B 76

C 77

A 78

C 79

B 80

C 81

C 82

B 83

B 84

B 85

B 86

B 87

C 88

C 89

C 90

C 91

C 92

C 93

C 94

B 95

C 96

C 97

C 98

C 99

C 100

A 101

B 102

B 103

B 104

B 105

C 106

C 107

C 108

C 109

A 110

B 111

C 112

C 113

C 114

C 115

C 116

C 117

C 118

C 119

C 120

C 121

C 122

C 123

C 124

B 125

C 126

C 127

B 128

B 129

B 130

A 131

C 132

C 133

C 134

C 135

C 136

C 137

C 138

B 139

B 140

A 141

B 142

A 143

A 144

A 145

C 146

C 147

B 148

C 149

C 150

C 151

C 152

A 153

B 154

A 155

B 156

B 157

B 158

B 159

A 160

B 161

C 162

C 163

B 164

A 165

B 166

A 167

B 168

C 169

B 170

B 171

C 172

C 173

A 174

A 175

A 176

B 177

B 178

A 179

B 180

B 181

C 182

B 183

A 184

C 185

B 186

C 187

C 188

B 189

B 190

B 191

B 192

B 193

C 194

C 195

C 196

C 197

B 198

A 199

A 200

A 201

B 202

A 203

C 204

C 205

B 206

C 207

C 208

C 209

B 210

B 211

C 212

B 213

A 214

C 215

C 216

C 217

C 218

A “A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotesinhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitoryconcentrations of greater than 500 nM.

TABLE 2 Biological Activity of Compounds of Formula I, where Ar¹-Acontains an amido or indolo group # Structure Avg IC50 219

A 220

C 221

B 222

A 223

A 224

B 225

A 226

A 227

C 228

A 229

A 230

C 231

B 232

A 233

B 234

B 235

A 236

A 237

A 238

A 239

A 240

B 241

B 242

B 243

B 244

C 245

C 246

A 247

B 248

A 249

A 250

A 251

A 252

A 253

C 254

B 255

A 256

A 257

C 258

C 259

C 260

B 261

A 262

C 263

A 264

C 265

C 266

C 267

A 268

B 269

A 270

C 271

C 272

A 273

A 274

A 275

A 276

C 277

A 278

A 279

A 280

A 281

B 282

C 283

A 284

B 285

C 286

A 287

A 288

A 289

A 290

A 291

A 292

A 293

A 294

B 295

A 296

B 297

B 298

B 299

C 300

A 301

A 302

B 303

A 304

A 305

A 306

A 307

A 308

B 309

C 310

A 311

B 312

A 313

C 314

C 315

C 316

A 317

B 318

B 319

A 320

A 321

A 322

A 323

B 324

B 325

C 326

A 327

A 328

A 329

A 330

A 331

A 332

B 333

A 334

A 335

A 336

C 337

A 338

A 339

A 340

A 341

A 342

A 343

C 344

C 345

A 346

A 347

A 348

A 349

A 350

A 351

B 352

A 353

A 354

A 355

A 356

A 357

A 358

B 359

B 360

A 361

B 362

A 363

C 364

A 365

B 366

A 367

A 368

A 369

A 370

A 371

B 372

B 373

A 374

A 375

A 376

A 377

C 378

B 379

B 380

B 381

A 382

A 383

A 384

B 385

A 386

C 387

B 388

B 389

C 390

B 391

B 392

B 393

A 394

A 395

B 396

B 397

C 398

B 399

B 400

B 401

A 402

A 403

B 404

A 405

A 406

A 407

A 408

A 409

A 410

A 411

B 412

A 413

B 414

A 415

A 416

B 417

C 418

B 419

C 420

C 421

A 422

A 423

A 424

A 425

B 426

A 427

C 428

B 429

B 430

B 431

A 432

B 433

A 434

A 435

A 436

B 437

A 438

A 439

C 440

A 441

A 442

A 443

A 444

A 445

A 446

A 447

A 448

A 449

A 450

A 451

A 452

A 453

A 454

A 455

A 456

B 457

A 458

A 459

A 460

A 461

A 462

B 463

A 464

A 465

B 466

A 467

A 468

A 469

A 470

A 471

C 472

A 473

A 474

A 475

A 476

A 477

A 478

A 479

C 480

A 481

A 482

A 483

A 484

A 485

B 486

C 487

A 488

C 489

C 490

B 491

C 492

B 493

A 494

A 495

C 496

C 497

A 498

B 499

B 500

A 501

B 502

A 503

B 504

B 505

A 506

B 507

C 508

C 509

C 510

C 511

C 512

C

A″ denotes inhibitory concentrations of 1 mM-200 nM, “B” denotesinhibitory concentrations of 200 nM-1000 nM, and “C” denotes inhibitoryconcentrations of greater than 100 nM.

Examples of compounds of the present invention are provided in thefollowing table.

TABLE 3 COMPOUND IC 50 E-1

C E-2

C E-4

C E-5

C E-6

C E-7

C E-8

B E-9

B E-10

A E-11

A E-12

B E-13

C E-14

C E-15

C E-16

A E-17

C E-18

C E-19

C E-20

A E-21

B E-22

C

Biological Activity of Compounds of Formula X—Activity of Benzamides

In the following table IC50's of several benzamides are compared. Here,“A” denotes inhibitory concentrations of 1 nM-100 nM, “B” denotesinhibitory concentrations of 100 nM-500 nM, and “C” denotes inhibitoryconcentrations of greater than 500 nM.

TABLE 4 COMPOUND IC 50

B

A

C

A

Biological Activity of Compounds of Formula I, where R′ is(CH₂)_(1 or 2)-G, where G is a Five- or Six-membered Ring or a 9- to14-member Fused Ring System

The following table shows the effects of substitution in R′. “A” denotesinhibitory concentrations of 1 nM-100 nM, “B” denotes inhibitoryconcentrations of 100 nM-500 nM, and “C” denotes inhibitoryconcentrations of greater than 500 nM.

Compound IC50 EC50

A A

A A

A A

B B

B B

A B

A A

A A

B B

B

A

B

C

A

C

B

A

B

B

1. A compound of formula I

where Ar¹ is phenyl, pyridyl, pyrimidyl, pyridazinyl, or triazinyl, inwhich all ring carbon atoms are optionally substituted with substituentsR₁, R₂, and R₃, which are selected independently from hydrogen; halogen;hydroxy; nitro; cyano; C₁-C₄ alkyl, optionally substituted with one tothree fluorine atoms; CH₃O; 2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O);CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or —S(O)₂NR₇R₈, where R₇ and R₈ are,independently, H, CH₃, or CH₃CH₂; and R₁ may also be 2-C(O)K, where K isselected from: —OJ, where J is isopropyl, cyclopropyl, cyclopentyl,dimethylamino, or methoxyethyl; —NHJ′ where J′ is methyl, ethyl,isopropyl, cyclopropyl, dimethylaminomethyl, or 3-methyl-2-yl-butanoicacid methyl ester; and —N(CH₃)₂; or 4-methylpiperzin-1-yl; or R₁ and R₂are attached to adjacent carbons and, together with the ring atoms towhich they are attached, form an additional, fused, five- orsix-membered ring, optionally containing one heteroatom, which ring maybe aromatic or aliphatic; A is O, S, CH₂, N₂, CO, NHCO, COCH₂, or CH₂CO;or Ar¹-A is

where the five-membered ring is fused to Ar¹ and Y is NH, S, or O; orAr¹-A is

where the dotted line represents an optional double bond, thefive-membered ring is fused to Ar¹, and R_(x) is selected fromsubstituents listed above for R₃; or Ar¹-A is

where the five-membered ring is fused to Ar¹, and R_(x) is selected fromsubstituents listed above for R₃; Ar² is phenyl, pyridyl, pyrimidyl,pyridazinyl, or triazinyl, where ring carbon atoms are optionallysubstituted with substituents R₄-R₆ which are selected independentlyfrom H, F, Cl, Br, CH₃, or CF₃; or Ar²—NH— is

where R_(y) is selected from substituents listed above for R₃; and R′ isOH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionallysubstituted with one to three groups selected independently fromhydroxy, halogen, C₁-C₃ alkoxy, and phenyl; —CH₂B or —CH₂CH₂B, where Bis selected from C₃₋₇ cycloalkyl, C₇-C₉ bicycloalkyl, pyridyl,piperazinyl, piperidinyl, N-morpholyl, tetrahydrofuryl, and naphthyl;C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl, where all cycloalkyl,bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,tetrahydrofuryl, and naphthyl groups are optionally substituted with oneto three groups selected independently from hydroxy, halogen, andmethyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2 and G is a five- orsix-membered ring or a 9-14-membered fused ring system, wherein eachring optionally contains 1-3 heteroatoms selected independently from O,N, and S; wherein each ring is optionally substituted with 1-3 groupsselected independently from the following: halogen, hydroxy, cyano, oxo,and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionallysubstituted with one to three halogen atoms; and wherein each ringoptionally contains one or more double bonds; or R′ is —CH(CH₂OH)CH₂D,where D is selected from imidazolyl, indolyl, carboxamido, phenyl,cyclohexyl, —CH₂SCH₃, and adamantin-1-yl.
 2. The compound of claim 1shown in formula II

where substituents R₁-R₆ and R′ are as defined for formula I and R* isH, except when R₁ and R₂ are both F, and when R₁ and R₂ are both F, R*is either H or Cl.
 3. The compound of claim 2 shown in formula III

wherein A is —O—, —CH₂—, —N₂—, —CH₂C(O)—, —S—, or —C(O)—; R₁, R₂, and R₃are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₄alkyl, optionally substituted with one to three fluorine atoms; CH₃O;2-methoxy ethenyl; (CH₃)₂N; CH₃OC(O); CH₃CH₂OC(O); NR₇R₈, —C(O)NR₇R₈; or—S(O)₂NR₇R₈, where R₇ and R₈ are, independently, H, CH₃, or CH₃CH₂; orR₁ and R₂ are attached to adjacent carbons and, together with the ringatoms to which they are attached, form an additional, fused, five- orsix-membered ring, optionally containing one heteroatom, which ring maybe aromatic or aliphatic; R₄-R₆ are, independently, H, F, Cl, Br, CH₃,or CF₃; R* is H, except when R₁ and R₂ are both F; when R₁ and R₂ areboth F, R* is either H or Cl; R′ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, saidC₁-C₆ alkyl groups optionally substituted with one to three groupsselected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl;—CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl, C₇-C₉bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl,where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionallysubstituted with one to three groups selected independently fromhydroxy, halogen, and methyl; or R′ is (CH₂)_(n)-G, where n is 1 or 2and G is a five- or six-membered ring or a 9-14-membered fused ringsystem, wherein each ring optionally contains 1-3 heteroatoms selectedindependently from O, N, and S; wherein each ring is optionallysubstituted with 1-3 groups selected independently from the following:halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkylgroup is optionally substituted with one to three halogen atoms; andwherein each ring optionally contains one or more double bonds.
 4. Thecompound of claim 1 shown in formula IV

wherein U, V, W, X, Y, and Z are, independently CH or N, provided thatU, V, W, X, Y, and Z are not all CH; A is —O—, —CH₂—, —N₂—, —NHC(O)—,—S—, or —C(O)—; R₁ and R₂ are, independently, hydrogen; halogen;hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms;CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ isOH; OC₁-C₆ alkyl; C₁-C₆ alkyl, optionally substituted with one to threegroups selected independently from hydroxy, halogen, C₁-C₃ alkoxy, andphenyl; —CH₂B or —CH₂CH₂B, where B is selected from C₃₋₇ cycloalkyl,C₇-C₉ bicycloalkyl, pyridyl, piperazinyl, piperidinyl, N-morpholyl,tetrahydrofuryl, and naphthyl; C₃-C₇ cycloalkyl; C₇-C₉ bicycloalkyl,where all cycloalkyl, bicycloalkyl, pyridyl, piperazinyl, piperidinyl,N-morpholyl, tetrahydrofuryl, and naphthyl groups are optionallysubstituted with one to three groups selected independently fromhydroxy, halogen, and methyl.
 5. The compound of claim 4 shown informula V

wherein Q₁ and Q₂ are, independently CH or N, provided that Q₁ and Q₂are not both CH; R₁ and R₂ are, independently, hydrogen; halogen;hydroxy; cyano; CH₃, optionally substituted with 1-3 fluorine atoms;CH₃O; (CH₃)₂N; CH₃OC(O); 2-methoxy ethenyl; and CH₃CH₂OC(O); and R′ isselected from C₁-C₆ alkyl, optionally substituted with 1-3 hydroxylgroups; cyclopropyl; —CH₂B; and —CH₂CH₂B, where B is selected from C₃₋₆cycloalkyl, phenyl, pyridyl, piperzin-1-yl, piperidin-1-yl, N-morpholyl,tetrahydrofuryl, and naphthyl.
 6. The compound of claim 1 shown informula VI

where Y is —NH—, —S— or —O—, and R′ is selected from1-hydroxy-isopropyl, 2-hydroxy-n-propyl, 2-hydroxy-ethyl, and2,3,-dihydroxy-n-propyl.
 7. The compound of claim 1 shown in Formula VII

where the dashed bond represents an optional double bond, and wheresymbols T-Z represent N, CH, or CR_(1, 2, or 4), provided that at mosttwo of W, X, Y, and Z and at most 2 of T, U, and V are N; where R₁-R₄are, independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl;2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅alkyl-C(O)O—; —NR₆R₇, —CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or—S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or any ofthe pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ are attached to adjacentcarbons and, together with the ring atoms to which they are attached,form an additional, fused, five- or six-membered ring, optionallycontaining one or two heteroatoms selected from O, N, and S, which ringmay be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkylgroups and all rings are optionally substituted with 1-3 halogen atoms,and all rings are also optionally substituted with 1-3 C₁-C₃ alkylgroups or trifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl,said C₁-C₆ alkyl groups optionally substituted with one to three groupsselected independently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl;or R₅ is —(CH₂)_(n)—B where n is 1 or 2 and B is a five- or six-memberedring or a 9- to 14-member fused ring system, wherein each ringoptionally contains 1-3 heteroatoms selected independently from O, N,and S; wherein each ring is optionally substituted with 1-3 groupsselected independently from the following: halogen, hydroxy, cyano, oxo,and C₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionallysubstituted with one to three halogen atoms; and wherein each ringoptionally contains one or more double bonds.
 8. The compound of claim 1shown in Formula VIII below, where the dashed bond represents anoptional double bond,

where R₁-R₄ are, independently, hydrogen; halogen; hydroxy; nitro;cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—;C₁-C₅ alkyl-C(O)O—; —NR₆R₇—CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—,or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, H or C₁-C₄ alkyl; or anyof the pairs R₁ and R₂, R₆ and R₇, or R₈ and R₉ are attached to adjacentcarbons and, together with the ring atoms to which they are attached,form an additional, fused, five- or six-membered ring, optionallycontaining one or two heteroatoms selected from O, N, and S, which ringmay be aromatic or aliphatic; wherein all alkyl, alkenyl, and cycloalkylgroups and all rings are optionally substituted with 1-3 halogen atoms;R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆ alkyl groups optionallysubstituted with one to three groups selected independently fromhydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is —(CH₂)_(n)—B wheren is 1 or 2 and B is a five- or six-membered ring or a 9- to 14-memberfused ring system, wherein each ring optionally contains 1-3 heteroatomsselected independently from O, N, and S; wherein each ring is optionallysubstituted with 1-3 groups selected independently from the following:halogen, hydroxy, cyano, oxo, and C₁-C₄ alkyl, wherein said C₁-C₄ alkylgroup is optionally substituted with one to three halogen atoms; andwherein each ring optionally contains one or more double bonds.
 9. Thecompound of claim 1 shown in formula IX, where the dashed bondrepresents an optional double bond, where R₁-R₅ are defined as forformula A, and where symbols W-Z represent N, CH, or CR_(1 or 2),provided that at least one of W-Z is N.


10. The compound of claim 1 shown in formula X

where M, Q, T, U, and V represent N, CH, or CR_(1, 2, or 3), providedthat no two nitrogen atoms are adjacent, where R₁-R₄ are, independently,hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl;C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl;CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR(R₇,—CH₂NR₆R₇, —NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, whereR₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ andR₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which theyare attached, form an additional, five- or six-membered ring, optionallycontaining one or two heteroatoms selected from O, N, and S, which ringmay be aromatic or aliphatic, and which ring is fused in the case of R₁and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl,wherein all alkyl, alkenyl, and cycloalkyl groups and all rings areoptionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, ortrifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is—(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring ora 9- to 14-member fused ring system, wherein each ring optionallycontains 1-3 heteroatoms selected independently from O, N, and S;wherein each ring is optionally substituted with 1-3 groups selectedindependently from the following: halogen, hydroxy, cyano, oxo, andC₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substitutedwith one to three halogen atoms; and wherein each ring optionallycontains one or more double bonds.
 11. The compound of claim 1 shown informula XI

where M, Q, T, U, V, W, X, Y, and Z represent N, CH, orCR_(1, 2, 3, or 4), where R₁-R₄ are, independently, hydrogen; halogen;hydroxy; nitro; cyano; C₁-C₆ alkyl; O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆alkynyl; C₁-C₆ cycloalkyl; 2-methoxy ethenyl; CH₃OC(O); CH₃CH₂OC(O);C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—; —NR₇, —CH₂NR₆R₇, —NH—C(O)—R₆,—C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, where R₆-R₉ are, independently, Hor C₁-C₄ alkyl; or any of the pairs R₁ and R₂; R₆ and R₇, or R₈ and R₉are attached to adjacent carbons and, together with the ring atoms towhich they are attached, form an additional, fused, five- orsix-membered ring, optionally containing one or two heteroatoms selectedfrom O, N, and S, which ring may be aromatic or aliphatic; and where R₁may also be isothiazolyl, isoxazolyl, oxazolyl, oxazolinyl,oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl,wherein all alkyl, alkenyl, and cycloalkyl groups and all rings areoptionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, ortrifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is—(CH₂)_(n)-G where n is 1 or 2 and G is a five- or six-membered ring ora 9- to 14-member fused ring system, wherein each ring optionallycontains 1-3 heteroatoms selected independently from O, N, and S;wherein each ring is optionally substituted with 1-3 groups selectedindependently from the following: halogen, hydroxy, cyano, oxo, andC₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substitutedwith one to three halogen atoms; and wherein each ring optionallycontains one or more double bonds.
 12. The compound of claim 11, whereM, Q, T, U, V, W, X, Y, and Z are all CH or CR_(1, 2, 3, or 4).
 13. Thecompound of claim 1 shown in formula XII

where the dashed bond represents an optional double bond, and wheresymbols L, T, U, V, and W-Z represent N, CH, or CR_(1, 2, or 4),provided that no two nitrogen atoms are adjacent, where R₁-R₄ are,independently, hydrogen; halogen; hydroxy; nitro; cyano; C₁-C₆ alkyl;O—C₁-C₆ alkyl; C₂-C₆ alkenyl; C₂-C₆ alkynyl; C₁-C₆ cycloalkyl; 2-methoxyethenyl; CH₃OC(O); CH₃CH₂OC(O); C₁-C₅ alkyl-C(O)—; C₁-C₅ alkyl-C(O)O—;—NR₆R₇—CH₂NR₆R₇—NH—C(O)—R₆, —C(O)NR₈R₉; CH₃S(O)₂—, or —S(O)₂NR₈R₉, whereR₆-R₉ are, independently, H or C₁-C₄ alkyl; or any of the pairs R₁ andR₂, R₆ and R₇, or R₈ and R₉, together with the ring atoms to which theyare attached, form an additional, five- or six-membered ring, optionallycontaining one or two heteroatoms selected from O, N, and S, which ringmay be aromatic or aliphatic, and which ring is fused in the case of R₁and R₂; and where R₁ may also be isothiazolyl, isoxazolyl, oxazolyl,oxazolinyl, oxazolidinyl, thiazolyl, thienyl, furyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, thiazolinyl, thiazolidinyl, isothiazolinyl,isothiazolidinyl, imidazolinyl, imidazolyl, pyridyl, tolyl, or phenyl,wherein all alkyl, alkenyl, and cycloalkyl groups and all rings areoptionally substituted with 1-3 halogen atoms, C₁-C₃ alkyl groups, ortrifluoromethyl groups; R₅ is OH; O—C₁-C₆ alkyl; C₁-C₆ alkyl, said C₁-C₆alkyl groups optionally substituted with one to three groups selectedindependently from hydroxy, halogen, C₁-C₃ alkoxy, and phenyl; or R₅ is—(CH₂)_(n)-G, where n is 1 or 2 and G is a five- or six-membered ring ora 9- to 14-member fused ring system, wherein each ring optionallycontains 1-3 heteroatoms selected independently from O, N, and S;wherein each ring is optionally substituted with 1-3 groups selectedindependently from the following: halogen, hydroxy, cyano, oxo, andC₁-C₄ alkyl, wherein said C₁-C₄ alkyl group is optionally substitutedwith one to three halogen atoms; and wherein each ring optionallycontains one or more double bonds.